Key Points
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Neuronal cell bodies in the mammalian CNS typically have more than a dozen distinct voltage-dependent conductances. The greater number of conductances compared to the squid axon is associated with much more complex firing patterns than can be produced by the squid axon.
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Action potential shapes and firing patterns differ widely among different types of neurons.
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One recognizable phenotype is that of fast-spiking neurons, which are capable of firing steadily at high frequencies and have narrow action potentials. This phenotype is typical of many interneurons and is associated with the expression of Kv3 family potassium channels.
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Some neurons with fast-spiking behaviour express resurgent sodium current, a component of tetrodotoxin-sensitive current that flows after the spike and promotes high-frequency firing.
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Most neurons have large calcium currents carried by multiple types of calcium channels. The calcium current is largest during the falling phase of the action potential but is often outweighed by calcium-activated potassium current, activated by extremely rapid coupling to calcium entry.
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Potassium channels commonly playing a major part in the repolarization of action potentials include Kv3 channels, IA (Kv4) channels, ID (Kv1) channels and large conductance calcium-activated potassium (BK) channels.
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Inactivation of potassium currents can produce frequency-dependent broadening of the action potential, which can produce synaptic facilitation. Potassium channels whose inactivation can lead to frequency-dependent spike broadening include BK channels and inactivating Kv1 family channels located in presynaptic terminals.
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Following the spike, many neurons have afterpotentials, including multiple types of afterhyperpolarizations with time courses lasting up to several seconds. Pyramidal neurons often have a prominent afterdepolarization which, if large enough, can lead to all-or-none bursting.
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Currents active at subthreshold voltages can greatly influence firing patterns and frequency. These include IA and ID potassium currents, steady-state “persistent” sodium current, T-type calcium current, and the hyperpolarization-activated cation current called Ih.
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The system of ionic currents that controls action potential shape and firing patterns in central neurons, although complex, has remarkable advantages for pursuing general problems in systems biology (such as robustness and redundancy): it has highly quantifiable elements, which are well-suited to mathematical modelling.
Abstract
The action potential of the squid giant axon is formed by just two voltage-dependent conductances in the cell membrane, yet mammalian central neurons typically express more than a dozen different types of voltage-dependent ion channels. This rich repertoire of channels allows neurons to encode information by generating action potentials with a wide range of shapes, frequencies and patterns. Recent work offers an increasingly detailed understanding of how the expression of particular channel types underlies the remarkably diverse firing behaviour of various types of neurons.
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References
Hodgkin, A. L. & Huxley, A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117, 500–544 (1952).
Hille, B. Ion Channels of Excitable Membranes (Sinauer, Sunderland, 2001).
Llinás, R. R. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242, 1654–1664 (1988). Seminal review/manifesto by a pioneer of CNS cellular electrophysiology, surveying the wide variety of intrinsic excitability of central neurons and emphasizing the intrinsic oscillatory behaviour of cells and circuits.
Guttman, R. & Barnhill, R. Oscillation and repetitive firing in squid axons. Comparison of experiments with computations. J. Gen. Physiol. 55, 104–118 (1970).
Connors, B. W. & Gutnick, M. J. Intrinsic firing patterns of diverse neocortical neurons. Trends Neurosci. 13, 99–104 (1990).
Erisir, A., Lau, D., Rudy, B. & Leonard, C. S. Function of specific K+ channels in sustained high-frequency firing of fast-spiking neocortical interneurons. J. Neurophysiol. 82, 2476–2489 (1999).
Bevan, M. D. & Wilson, C. J. Mechanisms underlying spontaneous oscillation and rhythmic firing in rat subthalamic neurons. J. Neurosci. 19, 7617–7628 (1999).
Nowak, L. G., Azouz, R., Sanchez-Vives, M. V., Gray, C. M. & McCormick, D. A. Electrophysiological classes of cat primary visual cortical neurons in vivo as revealed by quantitative analyses. J. Neurophysiol. 89, 1541–1566 (2003).
Tateno, T., Harsch, A. & Robinson, H. P. Threshold firing frequency-current relationships of neurons in rat somatosensory cortex: type 1 and type 2 dynamics. J. Neurophysiol. 92, 2283–2294 (2004).
Forti, L., Cesana, E., Mapelli, J. & D'Angelo, E. Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells. J. Physiol. 574, 711–729 (2006).
Hodgkin, A. L. The local electric changes associated with repetitive action in a non-medullated axon. J. Physiol. 107, 165–181 (1948).
Connor, J. A. Neural repetitive firing: a comparative study of membrane properties of crustacean walking leg axons. J. Neurophysiol. 38, 922–332 (1975).
Debanne, D. Information processing in the axon. Nature Rev. Neurosci. 5, 304–316 (2004).
Coetzee, W. A. et al. Molecular diversity of K+ channels. Ann. NY Acad. Sci. 868, 233–285 (1999).
McCormick, D. A., Connors, B. W., Lighthall, J. W. & Prince, D. A. Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J. Neurophysiol. 54, 782–806 (1985). Introduces 'regular-spiking', 'bursting' and 'fast-spiking' classifications of firing patterns of neocortical neurons, correlates firing patterns with spike shape, and identifies fast-spiking neocortical neurons as GABA-mediated interneurons.
Kawaguchi, Y. Physiological subgroups of nonpyramidal cells with specific morphological characteristics in layer II/III of rat frontal cortex. J. Neurosci. 15, 2638–2655 (1995).
Mountcastle, V. B., Talbot, W. H., Sakata, H. & Hyvarinen, J. Cortical neuronal mechanisms in flutter-vibration studied in unanesthetized monkeys. Neuronal periodicity and frequency discrimination. J. Neurophysiol. 32, 452–484 (1969).
Kawaguchi, Y. Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum. J. Neurosci. 13, 4908–4923 (1993).
Zhou, F. M. & Hablitz, J. J. Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties. J. Neurophysiol. 76, 651–667 (1996).
Descalzo, V. F., Nowak, L. G., Brumberg, J. C., McCormick, D. A. & Sanchez-Vives, M. V. Slow adaptation in fast-spiking neurons of visual cortex. J. Neurophysiol. 93, 1111–1118 (2005).
Du, J., Zhang, L., Weiser, M., Rudy, B. & McBain, C. J. Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus. J. Neurosci. 16, 506–518 (1996).
Massengill, J. L., Smith, M. A., Son, D. I. & O'Dowd, D. K. Differential expression of K4-AP currents and Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes. J. Neurosci. 17, 3136–3147 (1997).
Martina, M., Schultz, J. H., Ehmke, H., Monyer, H. & Jonas, P. Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus. J. Neurosci. 18, 8111–8125 (1998).
Lien, C. C., Martina, M., Schultz, J. H., Ehmke, H. & Jonas, P. Gating, modulation and subunit composition of voltage-gated K+ channels in dendritic inhibitory interneurones of rat hippocampus. J. Physiol. 538, 405–419 (2002).
Baranauskas, G., Tkatch, T., Nagata, K., Yeh, J. Z. & Surmeier, D. J. Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons. Nature Neurosci. 6, 258–266 (2003).
Lien, C. C. & Jonas, P. Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons. J. Neurosci. 23, 2058–2068 (2003). Uses the dynamic clamp technique to demonstrate that the Kv3-mediated potassium current speeds up firing and that deactivation kinetics are a crucial parameter for this effect.
Rudy, B. & McBain, C. J. Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing. Trends Neurosci. 24, 517–526 (2001). Comprehensive review of the correlation between the expression of Kv3 channels and the fast-spiking phenotype.
Southan, A. P. & Robertson, B. Electrophysiological characterization of voltage-gated K+ currents in cerebellar basket and purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals. J. Neurosci. 20, 114–122 (2000).
Martina, M., Yao, G. L. & Bean, B. P. Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. J. Neurosci. 23, 5698–5707 (2003).
McKay, B. E. & Turner, R. W. Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells. Eur. J. Neurosci. 20, 729–739 (2004).
Martina, M., Metz, A. E. & Bean, B. P. Voltage-dependent potassium currents during fast spikes of rat cerebellar Purkinje neurons: inhibition by BDS-I toxin. J. Neurophysiol. 97, 563–571 (2007).
Do, M. T. & Bean, B. P. Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron 39, 109–120 (2003).
Wigmore, M. A. & Lacey, M. G. A Kv3-like persistent, outwardly rectifying, Cs+-permeable, K+ current in rat subthalamic nucleus neurones. J. Physiol. 527, 493–506 (2000).
Brew, H. M. & Forsythe, I. D. Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse. J. Neurosci. 15, 8011–8022 (1995).
Wang, L. Y., Gan, L., Forsythe, I. D. & Kaczmarek, L. K. Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse auditory neurones. J. Physiol. 509, 183–194 (1998).
Ishikawa, T. et al. Distinct roles of Kv1 and Kv3 potassium channels at the calyx of Held presynaptic terminal. J. Neurosci. 23, 10445–10453 (2003).
Connors, B. W., Gutnick, M. J. & Prince, D. A. Electrophysiological properties of neocortical neurons in vitro. J. Neurophysiol. 48, 1302–1320 (1982). Classic description of all-or-none bursting, and of afterdepolarizations and action potential broadening, in neocortical pyramidal neurons.
Staff, N. P., Jung, H. Y., Thiagarajan, T., Yao, M. & Spruston, N. Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus. J. Neurophysiol. 84, 2398–2408 (2000).
Geiger, J. R. & Jonas, P. Dynamic control of presynaptic Ca2+ inflow by fast-inactivating K+ channels in hippocampal mossy fiber boutons. Neuron 28, 927–939 (2000). Remarkable sequence of current-clamp and voltage-clamp recordings from presynaptic terminals of mossy fibres and their postsynaptic targets, showing that presynaptic spikes are narrower than those in the cell body, that presynaptic spikes undergo frequency-dependent broadening due to inactivation of Kv1 family channels, and that spike broadening produces dramatic synaptic facilitation.
Coombs, J. S., Curtis, D. R. & Eccles, J. C. The interpretation of spike potentials of motoneurones. J. Physiol. 139, 198–231 (1957).
Grace, A. A. & Bunney, B. S. Intracellular and extracellular electrophysiology of nigral dopaminergic neurons—2. Action potential generating mechanisms and morphological correlates. Neuroscience 10, 317–331 (1983).
Hausser, M., Stuart, G., Racca, C. & Sakmann, B. Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron 15, 637–647 (1995).
Stuart, G., Schiller, J. & Sakmann, B. Action potential initiation and propagation in rat neocortical pyramidal neurons. J. Physiol. 505, 617–632 (1997). Uses double (and triple) patch pipette recordings in layer 5 pyramidal neurons to directly demonstrate that spikes are initiated in the axon before the soma — even with strong synaptic stimulation that first elicits regenerative potentials in dendrites. Also demonstrates back-propagation of axonal spikes into the dendritic tree.
Martina, M., Vida, I. & Jonas, P. Distal initiation and active propagation of action potentials in interneuron dendrites. Science 287, 295–300 (2000).
Palmer, L. M. & Stuart, G. J. Site of action potential initiation in layer 5 pyramidal neurons. J. Neurosci. 26, 1854–1863 (2006).
Khaliq, Z. M. & Raman, I. M. Relative contributions of axonal and somatic Na channels to action potential initiation in cerebellar Purkinje neurons. J. Neurosci. 26, 1935–1944 (2006).
Shu, Y., Duque, A., Yu, Y., Haider, B. & McCormick, D. A. Properties of action-potential initiation in neocortical pyramidal cells: evidence from whole cell axon recordings. J. Neurophysiol. 97, 746–760 (2007).
Raman, I. M. & Bean, B. P. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. J. Neurosci. 17, 4517–4526 (1997).
Kay, A. R. & Wong, R. K. Isolation of neurons suitable for patch-clamping from adult mammalian central nervous systems. J. Neurosci. Methods 16, 227–238 (1986).
Mitterdorfer, J. & Bean, B. P. Potassium currents during the action potential of hippocampal CA3 neurons. J. Neurosci. 22, 10106–10115 (2002).
Raman, I. M., Gustafson, A. E. & Padgett, D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J. Neurosci. 20, 9004–9016 (2000).
Shen, W., Hernandez-Lopez, S., Tkatch, T., Held, J. E. & Surmeier, D. J. Kv1.2-containing K+ channels regulate subthreshold excitability of striatal medium spiny neurons. J. Neurophysiol. 91, 1337–1349 (2004).
Chan, C. S., Shigemoto, R., Mercer, J. N. & Surmeier, D. J. HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. J. Neurosci. 24, 9921–9932 (2004).
Puopolo, M., Raviola, E. & Bean, B. P. Roles of subthreshold calcium current and sodium current in spontaneous firing of mouse midbrain dopamine neurons. J. Neurosci. 27, 645–656 (2007).
Nam, S. C. & Hockberger, P. E. Analysis of spontaneous electrical activity in cerebellar Purkinje cells acutely isolated from postnatal rats. J. Neurobiol. 33, 18–32 (1997).
Callaway, J. C. & Ross, W. N. Spatial distribution of synaptically activated sodium concentration changes in cerebellar Purkinje neurons. J. Neurophysiol. 77, 145–152 (1997).
Hausser, M. & Clark, B. A. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19, 665–678 (1997).
Jenerick, H. Phase plane trajectories of the muscle spike potential. Biophys. J. 3, 363–377 (1963).
Hodgkin, A. L., Huxley, A. F. & Katz, B. Measurement of current-voltage relations in the membrane of the giant axon of Loligo. J. Physiol. 116, 424–448 (1952).
Colbert, C. M. & Johnston, D. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons. J. Neurosci. 16, 6676–6686 (1996).
Clark, B. A., Monsivais, P., Branco, T., London, M. & Hausser, M. The site of action potential initiation in cerebellar Purkinje neurons. Nature Neurosci. 8, 137–139 (2005).
Martina, M. & Jonas, P. Functional differences in Na+ channel gating between fast-spiking interneurones and principal neurones of rat hippocampus. J. Physiol. 505, 593–603 (1997).
Maurice, N., Tkatch, T., Meisler, M., Sprunger, L. K. & Surmeier, D. J. D1/D5 dopamine receptor activation differentially modulates rapidly inactivating and persistent sodium currents in prefrontal cortex pyramidal neurons. J. Neurosci. 21, 2268–2277 (2001).
Ptak, K. et al. Sodium currents in medullary neurons isolated from the pre-Botzinger complex region. J. Neurosci. 25, 5159–5170 (2005).
Baranauskas, G. & Martina, M. Sodium currents activate without a Hodgkin-and-Huxley-type delay in central mammalian neurons. J. Neurosci. 26, 671–684 (2006).
Armstrong, C. M. & Bezanilla, F. Inactivation of the sodium channel. II. Gating current experiments. J. Gen. Physiol. 70, 567–590 (1977).
Bezanilla, F. & Armstrong, C. M. Inactivation of the sodium channel. I. Sodium current experiments. J. Gen. Physiol. 70, 549–566 (1977).
Engel, D. & Jonas, P. Presynaptic action potential amplification by voltage-gated Na+ channels in hippocampal mossy fiber boutons. Neuron 45, 405–417 (2005).
Neumcke, B. & Stampfli, R. Sodium currents and sodium-current fluctuations in rat myelinated nerve fibres. J. Physiol. 329, 163–184 (1982).
Neumcke, B., Schwarz, J. R. & Stampfli, R. A comparison of sodium currents in rat and frog myelinated nerve: normal and modified sodium inactivation. J. Physiol. 382, 175–191 (1987).
Naundorf, B., Wolf, F. & Volgushev, M. Unique features of action potential initiation in cortical neurons. Nature 440, 1060–1063 (2006).
McCormick, D. A., Shu, Y. & Yu, Y. Neurophysiology: Hodgkin and Huxley model — still standing? Nature 445, E1—E2 (2007).
Raman, I. M. & Bean, B. P. Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms. Biophys. J. 80, 729–737 (2001).
Grieco, T. M., Malhotra, J. D., Chen, C., Isom, L. L. & Raman, I. M. Open-channel block by the cytoplasmic tail of sodium channel β4 as a mechanism for resurgent sodium current. Neuron 45, 233–244 (2005). Presents evidence for a likely molecular mechanism underlying resurgent sodium currents.
Afshari, F. S. et al. Resurgent Na currents in four classes of neurons of the cerebellum. J. Neurophysiol. 92, 2831–2843 (2004).
Magistretti, J., Castelli, L., Forti, L. & D'Angelo, E. Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study. J. Physiol. 573, 83–106 (2006). State-of-the-art combination of voltage-clamp analysis of currents and modelling of firing, using a model with nine distinct conductances including an allosteric sodium channel model.
Enomoto, A., Han, J. M., Hsiao, C. F., Wu, N. & Chandler, S. H. Participation of sodium currents in burst generation and control of membrane excitability in mesencephalic trigeminal neurons. J. Neurosci. 26, 3412–3422 (2006).
Leao, R. N., Naves, M. M., Leao, K. E. & Walmsley, B. Altered sodium currents in auditory neurons of congenitally deaf mice. Eur. J. Neurosci. 24, 1137–1146 (2006).
Cummins, T. R., Dib-Hajj, S. D., Herzog, R. I. & Waxman, S. G. Nav1.6 channels generate resurgent sodium currents in spinal sensory neurons. FEBS Lett. 579, 2166–2170 (2005).
Khaliq, Z. M., Gouwens, N. W. & Raman, I. M. The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. J. Neurosci. 23, 4899–4912 (2003).
Sah, P. & McLachlan, E. M. Potassium currents contributing to action potential repolarization and the afterhyperpolarization in rat vagal motoneurons. J. Neurophysiol. 68, 1834–1841 (1992).
Sah, P. Ca2+-activated K+ currents in neurones: types, physiological roles and modulation. Trends Neurosci. 19, 150–154 (1996).
Shao, L. R., Halvorsrud, R., Borg-Graham, L. & Storm, J. F. The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells. J. Physiol. 521, 135–146 (1999).
Sah, P. & Faber, E. S. Channels underlying neuronal calcium-activated potassium currents. Prog. Neurobiol. 66, 345–353 (2002).
Faber, E. S. & Sah, P. Physiological role of calcium-activated potassium currents in the rat lateral amygdala. J. Neurosci. 22, 1618–1628 (2002).
Faber, E. S. & Sah, P. Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala. J. Physiol. 552, 483–497 (2003).
Sun, X., Gu, X. Q. & Haddad, G. G. Calcium influx via L- and N-type calcium channels activates a transient large-conductance Ca2+-activated K+ current in mouse neocortical pyramidal neurons. J. Neurosci. 23, 3639–3648 (2003).
Goldberg, J. A. & Wilson, C. J. Control of spontaneous firing patterns by the selective coupling of calcium currents to calcium-activated potassium currents in striatal cholinergic interneurons. J. Neurosci. 25, 10230–10238 (2005).
Storm, J. F. Potassium currents in hippocampal pyramidal cells. Prog. Brain Res. 83, 161–187 (1990).
Chen, W., Zhang, J. J., Hu, G. Y. & Wu, C. P. Different mechanisms underlying the repolarization of narrow and wide action potentials in pyramidal cells and interneurons of cat motor cortex. Neuroscience 73, 57–68 (1996).
Lancaster, B. & Nicoll, R. A. Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J. Physiol. 389, 187–203 (1987).
Storm, J. F. Intracellular injection of a Ca2+ chelator inhibits spike repolarization in hippocampal neurons. Brain Res. 435, 387–392 (1987).
Marrion, N. V. & Tavalin, S. J. Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature 395, 900–905 (1998).
Grunnet, M. & Kaufmann, W. A. Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain. J. Biol. Chem. 279, 36445–36453 (2004).
Berkefeld, H. et al. BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling. Science 314, 615–620 (2006).
Muller, A., Kukley, M., Uebachs, M., Beck, H. & Dietrich, D. Nanodomains of single Ca2+ channels contribute to action potential repolarization in cortical neurons. J. Neurosci. 27, 483–495 (2007).
Bennett, B. D., Callaway, J. C. & Wilson, C. J. Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons. J. Neurosci. 20, 8493–8503 (2000). A combination of current-clamp, voltage-clamp and calcium imaging to determine the ionic mechanism of pacemaking in tonically active cholinergic neurons of the striatum.
Taddese, A. & Bean, B. P. Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons. Neuron 33, 587–600 (2002).
Viana, F., Bayliss, D. A. & Berger, A. J. Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons. J. Neurophysiol. 69, 2150–2163 (1993).
Williams, S., Serafin, M., Muhlethaler, M. & Bernheim, L. Distinct contributions of high- and low-voltage-activated calcium currents to afterhyperpolarizations in cholinergic nucleus basalis neurons of the guinea pig. J. Neurosci. 17, 7307–7315 (1997).
Pineda, J. C., Waters, R. S. & Foehring, R. C. Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J. Neurophysiol. 79, 2522–2534 (1998).
Wolfart, J. & Roeper, J. Selective coupling of T-type calcium channels to SK potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons. J. Neurosci. 22, 3404–3413 (2002).
Hallworth, N. E., Wilson, C. J. & Bevan, M. D. Apamin-sensitive small conductance calcium-activated potassium channels, through their selective coupling to voltage-gated calcium channels, are critical determinants of the precision, pace, and pattern of action potential generation in rat subthalamic nucleus neurons in vitro. J. Neurosci. 23, 7525–7542 (2003).
Womack, M. D., Chevez, C. & Khodakhah, K. Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons. J. Neurosci. 24, 8818–8822 (2004).
Nedergaard, S. A Ca2+-independent slow afterhyperpolarization in substantia nigra compacta neurons. Neuroscience 125, 841–852 (2004).
Wolfart, J., Neuhoff, H., Franz, O. & Roeper, J. Differential expression of the small-conductance, calcium-activated potassium channel SK3 is critical for pacemaker control in dopaminergic midbrain neurons. J. Neurosci. 21, 3443–3456 (2001).
Walter, J. T., Alvina, K., Womack, M. D., Chevez, C. & Khodakhah, K. Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nature Neurosci. 9, 389–397 (2006).
Raman, I. M. & Bean, B. P. Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J. Neurosci. 19, 1663–1674 (1999).
Jackson, A. C., Yao, G. L. & Bean, B. P. Mechanism of spontaneous firing in dorsomedial suprachiasmatic nucleus neurons. J. Neurosci. 24, 7985–7998 (2004).
Llinás, R., Sugimori, M. & Simon, S. M. Transmission by presynaptic spike-like depolarization in the squid giant synapse. Proc. Natl Acad. Sci. USA 79, 2415–2419 (1982).
Jackson, M. B., Konnerth, A. & Augustine, G. J. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals. Proc. Natl Acad. Sci. USA 88, 380–384 (1991).
Borst, J. G. & Sakmann, B. Effect of changes in action potential shape on calcium currents and transmitter release in a calyx-type synapse of the rat auditory brainstem. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 347–355 (1999). Action potential clamp experiments on presynaptic terminals (calyx of Held) showing that calcium channels are activated with high efficacy by action potentials.
Bischofberger, J., Geiger, J. R. & Jonas, P. Timing and efficacy of Ca2+ channel activation in hippocampal mossy fiber boutons. J. Neurosci. 22, 10593–10602 (2002).
Yang, Y. M. & Wang, L. Y. Amplitude and kinetics of action potential-evoked Ca2+ current and its efficacy in triggering transmitter release at the developing calyx of held synapse. J. Neurosci. 26, 5698–5708 (2006).
Fernandez, F. R., Mehaffey, W. H., Molineux, M. L. & Turner, R. W. High-threshold K+ current increases gain by offsetting a frequency-dependent increase in low-threshold K+ current. J. Neurosci. 25, 363–371 (2005).
Akemann, W. & Knopfel, T. Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons. J. Neurosci. 26, 4602–4612 (2006).
Storm, J. F. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells. J. Physiol. 385, 733–759 (1987). Analysis using pharmacology and ionic substitution of the potassium currents underlying spike repolarization, fast, medium and slow afterhyperpolarizations in CA1 pyramidal neurons.
Locke, R. E. & Nerbonne, J. M. Three kinetically distinct Ca2+-independent depolarization-activated K+ currents in callosal-projecting rat visual cortical neurons. J. Neurophysiol. 78, 2309–2320 (1997).
Locke, R. E. & Nerbonne, J. M. Role of voltage-gated K+ currents in mediating the regular-spiking phenotype of callosal-projecting rat visual cortical neurons. J. Neurophysiol. 78, 2321–2335 (1997).
Golding, N. L., Jung, H. Y., Mickus, T. & Spruston, N. Dendritic calcium spike initiation and repolarization are controlled by distinct potassium channel subtypes in CA1 pyramidal neurons. J. Neurosci. 19, 8789–8798 (1999).
Kang, J., Huguenard, J. R. & Prince, D. A. Voltage-gated potassium channels activated during action potentials in layer V neocortical pyramidal neurons. J. Neurophysiol. 83, 70–80 (2000).
Wu, R. L. & Barish, M. E. Two pharmacologically and kinetically distinct transient potassium currents in cultured embryonic mouse hippocampal neurons. J. Neurosci. 12, 2235–2246 (1992).
Wu, R. L. & Barish, M. E. Modulation of a slowly inactivating potassium current, ID, by metabotropic glutamate receptor activation in cultured hippocampal pyramidal neurons. J. Neurosci. 19, 6825–6837 (1999).
Riazanski, V. et al. Functional and molecular analysis of transient voltage-dependent K+ currents in rat hippocampal granule cells. J. Physiol. 537, 391–406 (2001).
Kim, J., Wei, D. S. & Hoffman, D. A. Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones. J. Physiol. 569, 41–57 (2005).
Yuan, W., Burkhalter, A. & Nerbonne, J. M. Functional role of the fast transient outward K+ current IA in pyramidal neurons in (rat) primary visual cortex. J. Neurosci. 25, 9185–9194 (2005).
Shibata, R. et al. A-type K+ current mediated by the Kv4 channel regulates the generation of action potential in developing cerebellar granule cells. J. Neurosci. 20, 4145–4155 (2000).
Sheng, M., Tsaur, M. L., Jan, Y. N. & Jan, L. Y. Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron 9, 271–284 (1992).
Storm, J. F. Temporal integration by a slowly inactivating K+ current in hippocampal neurons. Nature 336, 379–381 (1988). Description of I D as a subthreshold, slowly inactivating potassium current sensitive to low concentrations of 4-aminopyridine and distinct from I A and delayed-rectifier potassium currents.
Stansfeld, C. E., Marsh, S. J., Halliwell, J. V. & Brown, D. A. 4-Aminopyridine and dendrotoxin induce repetitive firing in rat visceral sensory neurones by blocking a slowly inactivating outward current. Neurosci. Lett. 64, 299–304 (1986).
Bekkers, J. M. & Delaney, A. J. Modulation of excitability by α-dendrotoxin-sensitive potassium channels in neocortical pyramidal neurons. J. Neurosci. 21, 6553–6560 (2001).
Guan, D., Lee, J. C., Higgs, M. H., Spain, W. J. & Foehring, R. C. Functional roles of Kv1 channels in neocortical pyramidal neurons. J. Neurophysiol. 97, 1931–1940 (2007).
Spain, W. J., Schwindt, P. C. & Crill, W. E. Two transient potassium currents in layer V pyramidal neurones from cat sensorimotor cortex. J. Physiol. 434, 591–607 (1991).
Ma, M. & Koester, J. Consequences and mechanisms of spike broadening of R20 cells in Aplysia californica. J. Neurosci. 15, 6720–6734 (1995).
Ma, M. & Koester, J. The role of K+ currents in frequency-dependent spike broadening in Aplysia R20 neurons: a dynamic-clamp analysis. J. Neurosci. 16, 4089–4101 (1996). Combines the use of action potential clamp and dynamic clamp to analyse the changes in ionic currents underlying frequency-dependent spike broadening in an Aplysia neuron.
Connor, J. A. & Stevens, C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J. Physiol. 213, 21–30 (1971).
Connor, J. A. & Stevens, C. F. Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma. J. Physiol. 213, 31–53 (1971). Classic pair of papers describing I A in a snail neuron and using a computer model to analyse how it enables steady low-frequency firing.
Dodson, P. D., Barker, M. C. & Forsythe, I. D. Two heteromeric Kv1 potassium channels differentially regulate action potential firing. J. Neurosci. 22, 6953–6961 (2002).
McKay, B. E., Molineux, M. L., Mehaffey, W. H. & Turner, R. W. Kv1 K+ channels control Purkinje cell output to facilitate postsynaptic rebound discharge in deep cerebellar neurons. J. Neurosci. 25, 1481–1492 (2005).
Golomb, D., Yue, C. & Yaari, Y. Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study. J. Neurophysiol. 96, 1912–1926 (2006).
Crill, W. E. Persistent sodium current in mammalian central neurons. Annu. Rev. Physiol. 58, 349–362 (1996).
Brumberg, J. C., Nowak, L. G. & McCormick, D. A. Ionic mechanisms underlying repetitive high-frequency burst firing in supragranular cortical neurons. J. Neurosci. 20, 4829–4843 (2000).
Hu, H., Vervaeke, K. & Storm, J. F. Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells. J. Physiol. 545, 783–805 (2002).
Astman, N., Gutnick, M. J. & Fleidervish, I. A. Persistent sodium current in layer 5 neocortical neurons is primarily generated in the proximal axon. J. Neurosci. 26, 3465–3473 (2006).
Vervaeke, K., Hu, H., Graham, L. J. & Storm, J. F. Contrasting effects of the persistent Na+ current on neuronal excitability and spike timing. Neuron 49, 257–270 (2006). Clear illustration of the context-sensitivity of the role of a given conductance, using dynamic clamp and an unusually detailed model of firing (incorporating 11 voltage-dependent conductances) to analyse counter-intuitive effects of a persistent sodium current on the firing patterns of CA1 pyramidal neurons.
Maurice, N. et al. D2 dopamine receptor-mediated modulation of voltage-dependent Na+ channels reduces autonomous activity in striatal cholinergic interneurons. J. Neurosci. 24, 10289–10301 (2004). Combines current clamp, voltage clamp, and modelling to show that modest changes in sodium channel gating produced by dopamine can produce surprisingly large effects on the frequency of spontaneous firing.
Magistretti, J. & Alonso, A. Biophysical properties and slow voltage-dependent inactivation of a sustained sodium current in entorhinal cortex layer-II principal neurons: a whole-cell and single-channel study. J. Gen. Physiol. 114, 491–509 (1999).
Magistretti, J. & Alonso, A. Fine gating properties of channels responsible for persistent sodium current generation in entorhinal cortex neurons. J. Gen. Physiol. 120, 855–873 (2002).
Azouz, R., Jensen, M. S. & Yaari, Y. Ionic basis of spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells. J. Physiol. 492, 211–223 (1996).
Gutfreund, Y., yarom, Y. & Segev, I. Subthreshold oscillations and resonant frequency in guinea-pig cortical neurons: physiology and modelling. J. Physiol. 483, 621–640 (1995).
Hutcheon, B., Miura, R. M. & Puil, E. Subthreshold membrane resonance in neocortical neurons. J. Neurophysiol. 76, 683–697 (1996).
White, J. A., Klink, R., Alonso, A. & Kay, A. R. Noise from voltage-gated ion channels may influence neuronal dynamics in the entorhinal cortex. J. Neurophysiol. 80, 262–269 (1998).
Wu, N. et al. Persistent sodium currents in mesencephalic v neurons participate in burst generation and control of membrane excitability. J. Neurophysiol. 93, 2710–2722 (2005).
Llinás, R. & Yarom, Y. Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductances. J. Physiol. 315, 549–567 (1981).
Jahnsen, H. & Llinás, R. Ionic basis for the electro-responsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J. Physiol. 349, 227–247 (1984).
Williams, S. R., Toth, T. I., Turner, J. P., Hughes, S. W. & Crunelli, V. The 'window' component of the low threshold Ca2+ current produces input signal amplification and bistability in cat and rat thalamocortical neurones. J. Physiol. 505, 689–705 (1997).
Henze, D. A. & Buzsaki, G. Action potential threshold of hippocampal pyramidal cells in vivo is increased by recent spiking activity. Neuroscience 105, 121–130 (2001).
de Polavieja, G. G., Harsch, A., Kleppe, I., Robinson, H. P. & Juusola, M. Stimulus history reliably shapes action potential waveforms of cortical neurons. J. Neurosci. 25, 5657–5665 (2005).
Korngreen, A., Kaiser, K. M. & Zilberter, Y. Subthreshold inactivation of voltage-gated K+ channels modulates action potentials in neocortical bitufted interneurones from rats. J. Physiol. 562, 421–437 (2005).
Alle, H. & Geiger, J. R. Combined analog and action potential coding in hippocampal mossy fibers. Science 311, 1290–1293 (2006).
Shu, Y., Hasenstaub, A., Duque, A., Yu, Y. & McCormick, D. A. Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential. Nature 441, 761–765 (2006). References 160 and 161 demonstrate, in two types of glutamatergic neurons, that the electrotonic length constant of the axon is long enough (400–450 μm) that changes in membrane potential at the soma can influence membrane potential at presynaptic terminals.
Goldstein, S. A., Bockenhauer, D., O'Kelly, I. & Zilberberg, N. Potassium leak channels and the KCNK family of two-P-domain subunits. Nature Rev. Neurosci. 2, 175–184 (2001).
Meuth, S. G. et al. Membrane resting potential of thalamocortical relay neurons is shaped by the interaction among TASK3 and HCN2 channels. J. Neurophysiol. 96, 1517–1529 (2006).
Mathie, A. Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. J. Physiol. 578, 377–385 (2007).
Berg, A. P. & Bayliss, D. A. Striatal cholinergic interneurons express a receptor-insensitive homomeric TASK-3-like background K+ current. J. Neurophysiol. 97, 1546–1552 (2007).
Eggermann, E. et al. The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarization. J. Neurosci. 23, 1557–1562 (2003).
Pape, H. C. Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. Annu. Rev. Physiol. 58, 299–327 (1996).
Robinson, R. B. & Siegelbaum, S. A. Hyperpolarization-activated cation currents: from molecules to physiological function. Annu. Rev. Physiol. 65, 453–480 (2003).
McCormick, D. A. & Pape, H. C. Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones. J. Physiol. 431, 291–318 (1990).
Maccaferri, G. & McBain, C. J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones. J. Physiol. 497, 119–130 (1996).
Wilson, C. J. & Callaway, J. C. Coupled oscillator model of the dopaminergic neuron of the substantia nigra. J. Neurophysiol. 83, 3084–3100 (2000).
Stocker, M. Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nature Rev. Neurosci. 5, 758–770 (2004).
Pedarzani, P. et al. Specific enhancement of SK channel activity selectively potentiates the afterhyperpolarizing current IAHP and modulates the firing properties of hippocampal pyramidal neurons. J. Biol. Chem. 280, 41404–41411 (2005).
Gu, N., Vervaeke, K., Hu, H. & Storm, J. F. Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells. J. Physiol. 566, 689–715 (2005).
Lawrence, J. J. et al. Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons. J. Neurosci. 26, 12325–12338 (2006).
Womack, M. D. & Khodakhah, K. Characterization of large conductance Ca2+-activated K+ channels in cerebellar Purkinje neurons. Eur. J. Neurosci. 16, 1214–1222 (2002).
Edgerton, J. R. & Reinhart, P. H. Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function. J. Physiol. 548, 53–69 (2003).
Vogalis, F., Storm, J. F. & Lancaster, B. SK channels and the varieties of slow after-hyperpolarizations in neurons. Eur. J. Neurosci. 18, 3155–3166 (2003).
Bond, C. T. et al. Small conductance Ca2+-activated K+ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents. J. Neurosci. 24, 5301–5306 (2004).
Villalobos, C., Shakkottai, V. G., Chandy, K. G., Michelhaugh, S. K. & Andrade, R. SKCa channels mediate the medium but not the slow calcium-activated afterhyperpolarization in cortical neurons. J. Neurosci. 24, 3537–3542 (2004).
Shah, M. M., Javadzadeh-Tabatabaie, M., Benton, D. C., Ganellin, C. R. & Haylett, D. G. Enhancement of hippocampal pyramidal cell excitability by the novel selective slow-afterhyperpolarization channel blocker 3-(triphenylmethylaminomethyl)pyridine (UCL2077). Mol. Pharmacol. 70, 1494–1502 (2006).
Wong, R. K. & Prince, D. A. Afterpotential generation in hippocampal pyramidal cells. J. Neurophysiol. 45, 86–97 (1981).
White, G., Lovinger, D. M. & Weight, F. F. Transient low-threshold Ca2+ current triggers burst firing through an afterdepolarizing potential in an adult mammalian neuron. Proc. Natl Acad. Sci. USA 86, 6802–6806 (1989).
Jensen, M. S., Azouz, R. & Yaari, Y. Spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells. J. Physiol. 492, 199–210 (1996).
Swensen, A. M. & Bean, B. P. Ionic mechanisms of burst firing in dissociated Purkinje neurons. J. Neurosci. 23, 9650–9663 (2003).
Metz, A. E., Jarsky, T., Martina, M. & Spruston, N. R-type calcium channels contribute to afterdepolarization and bursting in hippocampal CA1 pyramidal neurons. J. Neurosci. 25, 5763–5773 (2005).
Haj-Dahmane, S. & Andrade, R. Calcium-activated cation nonselective current contributes to the fast afterdepolarization in rat prefrontal cortex neurons. J. Neurophysiol. 78, 1983–1989 (1997).
Wong, R. K. & Stewart, M. Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea-pig hippocampus. J. Physiol. 457, 675–687 (1992).
Andreasen, M. & Lambert, J. D. Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus. J. Physiol. 483, 421–441 (1995).
Magee, J. C. & Carruth, M. Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons. J. Neurophysiol. 82, 1895–1901 (1999).
Williams, S. R. & Stuart, G. J. Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons. J. Physiol. 521, 467–482 (1999). Incisive analysis of the mechanism of all-or-none bursting in layer 5 pyramidal neurons, showing the crucial role of activation of dendritic sodium channels and calcium channels.
D'Angelo, E. et al. Theta-frequency bursting and resonance in cerebellar granule cells: experimental evidence and modeling of a slow k+-dependent mechanism. J. Neurosci. 21, 759–770 (2001).
Achard, P. & De Schutter, E. Complex parameter landscape for a complex neuron model. PLoS Comput. Biol. 2, e94 (2006).
Goldman, M. S., Golowasch, J., Marder, E. & Abbott, L. F. Global structure, robustness, and modulation of neuronal models. J. Neurosci. 21, 5229–5238 (2001). Remarkable demonstration — using modelling together with dynamic clamp experiments — that nearly identical bursting behaviour can be produced by highly variable combinations of levels of five conductances, even when small changes in a given conductance can modulate firing.
Golowasch, J., Goldman, M. S., Abbott, L. F. & Marder, E. Failure of averaging in the construction of a conductance-based neuron model. J. Neurophysiol. 87, 1129–1131 (2002).
Marder, E. & Goaillard, J. M. Variability, compensation and homeostasis in neuron and network function. Nature Rev. Neurosci. 7, 563–574 (2006).
Swensen, A. M. & Bean, B. P. Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. J. Neurosci. 25, 3509–3520 (2005).
Sharp, A. A., O'Neil, M. B., Abbott, L. F. & Marder, E. Dynamic clamp: computer-generated conductances in real neurons. J. Neurophysiol. 69, 992–995 (1993).
Robinson, H. P. & Kawai, N. Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J. Neurosci. Methods 49, 157–165 (1993).
Prinz, A. A., Abbott, L. F. & Marder, E. The dynamic clamp comes of age. Trends Neurosci. 27, 218–224 (2004).
Goldman, L. & Schauf, C. L. Inactivation of the sodium current in Myxicola giant axons. Evidence for coupling to the activation process. J. Gen. Physiol. 59, 659–675 (1972).
Aldrich, R. W., Corey, D. P. & Stevens, C. F. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 306, 436–441 (1983).
Vandenberg, C. A. & Bezanilla, F. A sodium channel gating model based on single channel, macroscopic ionic, and gating currents in the squid giant axon. Biophys. J. 60, 1511–1533 (1991).
Kuo, C. C. & Bean, B. P. Na+ channels must deactivate to recover from inactivation. Neuron 12, 819–829 (1994).
Serrano, J. R., Perez-Reyes, E. & Jones, S. W. State-dependent inactivation of the alpha1G T-type calcium channel. J. Gen. Physiol. 114, 185–201 (1999).
Beck, E. J., Bowlby, M., An, W. F., Rhodes, K. J. & Covarrubias, M. Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein. J. Physiol. 538, 691–706 (2002).
Acknowledgements
I am grateful to M. Puopolo, M. Martina, B. Carter and A. Swensen for permission to use their unpublished data, and to them, Z. Khaliq and A. Jackson for much helpful discussion. Supported by the National Institute of Neurological Diseases and Stroke (NS36855).
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Glossary
- Heterologous expression
-
Expression of protein molecules by the injection of complementary RNA into the cytoplasm (or complementary DNA into the nucleus) of host cells that do not normally express the proteins, such as Xenopus oocytes or mammalian cell lines.
- Spike
-
Another term for an action potential (especially the portion with the most rapidly changing voltage).
- Projection neurons
-
Neurons with relatively long axons that project out of a local circuit (distinct from interneurons).
- Bursting
-
The firing of a rapid series of several action potentials with very short (less than ∼5 ms) interspike intervals.
- Adaptation
-
Slowing or cessation of firing during a maintained stimulus.
- Initial segment
-
The slender initial region of an axon where it originates from an axon hillock of the cell body (or sometimes from a major dendrite), characterized by the fasciculation of microtubules.
- Node of Ranvier
-
Interruption of the myelin sheath in a myelinated nerve fibre.
- Outside-out patch
-
A variant of the patch-clamp technique in which a patch of plasma membrane covers the tip of the electrode, with the outside of the membrane exposed to the bathing solution.
- Activation
-
Conformational change of a channel molecule from a closed (non-conducting) to an open (conducting) state (for voltage-dependent channels, this is usually by depolarization of the membrane).
- Subthreshold voltages
-
Voltages negative to the threshold voltage (Box 1) for action potential firing (which is typically in the range of −55 mV to −40 mV in mammalian central neurons).
- Tetrodotoxin
-
(TTX). Alkaloid toxin derived from Fugu puffer fish that is a potent and highly selective blocker of voltage-dependent sodium channels.
- Inactivation
-
Conformational change of a channel molecule to a closed state that differs from the closed 'resting' state in that the channel cannot be opened (for example, by further depolarization).
- 4-aminopyridine
-
Potassium channel blocker that inhibits some potassium channels (including Kv3 family channels and a subset of Kv1 family subunits) with a high relative potency and others (such as Kv4 channels) more weakly, or not all.
- Tetraethylammonium ion
-
(TEA). When applied externally, this blocks some types of voltage-activated potassium channels (notably BK and Kv3 family channels) and not others.
- Delayed-rectifier current
-
Depolarization-activated potassium current similar to that of the squid axon, with relatively slow activation and minimal (or very slow) inactivation.
- e-fold
-
Measure of steepness of voltage-dependent activation, associated with a description by the Boltzmann function; e-fold increase is a 2.72-fold increase.
- Midpoint
-
Voltage at which activation is half-maximal.
- Rebound bursting
-
Firing of a burst of action potentials when a hyperpolarizing influence (such as inhibitory postsynaptic potential) is terminated.
- Electrotonic length constant
-
Measure of the distance over which a voltage change imposed at one point in a cable-like structure decays to 1/e (∼37%).
- Pacemaking neurons
-
Neurons that fire spontaneous action potentials in a regular, rhythmic manner.
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Bean, B. The action potential in mammalian central neurons. Nat Rev Neurosci 8, 451–465 (2007). https://doi.org/10.1038/nrn2148
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DOI: https://doi.org/10.1038/nrn2148
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