Abstract
Neurons with the capacity to discharge at high rates—'fast-spiking' (FS) neurons—are critical participants in central motor and sensory circuits. It is widely accepted that K+ channels with Kv3.1 or Kv3.2 subunits underlie fast, delayed-rectifier (DR) currents that endow neurons with this FS ability. Expression of these subunits in heterologous systems, however, yields channels that open at more depolarized potentials than do native Kv3 family channels, suggesting that they differ. One possibility is that native channels incorporate a subunit that modifies gating. Molecular, electrophysiological and pharmacological studies reported here suggest that a splice variant of the Kv3.4 subunit coassembles with Kv3.1 subunits in rat brain FS neurons. Coassembly enhances the spike repolarizing efficiency of the channels, thereby reducing spike duration and enabling higher repetitive spike rates. These results suggest that manipulation of K3.4 subunit expression could be a useful means of controlling the dynamic range of FS neurons.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hodgkin, A.L. & Huxley, A.F. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. J. Physiol. 116, 449–472 (1952).
Hodgkin, A.L. & Huxley, A.F. The components of membrane conductance in the giant axon of Loligo. J. Physiol. 116, 473–496 (1952).
Rudy, B. & McBain, C.J. Kv3 channels: voltage-gated channels designed for high-frequency repetitive firing. Trends Neurosci. 24, 517–526 (2001).
Coetzee, W.A. et al. Molecular diversity of K+ channels. Ann. NY Acad. Sci. 868, 233–285 (1999).
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).
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).
Lenz, S., Perney, T.M., Qin, Y., Robbins, E. & Chesselet, M.F. GABAergic interneurons of the striatum express the Shaw-like potassium channel Kv3.1. Synapse 18, 55–66 (1994).
Weiser, M. et al. Differential expression of Shaw-related K+ channels in the rat central nervous system. J. Neurosci. 14, 949–972 (1994).
Weiser, M. et al. The potassium channel subunit KV3.1b is localized to somatic and axonal membranes of specific populations of CNS neurons. J. Neurosci. 15, 4298–4314 (1995).
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).
Baranauskas, G., Tkatch, T. & Surmeier, D.J. Delayed-rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K+ channels. J. Neurosci. 19, 6394–6404 (1999).
Vega-Saenz de Miera, E. et al. Shaw-related K+ channels in mammals. Handbook of Membrane Channels C. Peracchia 41–78 (Academic, New York, 1994).
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).
Wigmore, M.A. & Lacey, M.G. A Kv3-like persistent, outwardly rectifying, Cs+-permeable, K+ current in rat subthalamic nucleus neurons. J. Physiol. 527, 493–506 (2000).
Schroter, K.H. et al. Cloning and functional expression of a TEA-sensitive A-type potassium channel from rat brain. FEBS Lett. 278, 211–216 (1991).
Rettig, J. et al. Characterization of a Shaw-related potassium channel family in rat brain. EMBO J. 11, 2473–2486 (1992).
Diochot, S., Schweitz, H., Beress, L. & Lazdunski, M. Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4. J. Biol. Chem. 273, 6744–6749 (1998).
Thompson, S. Aminopyridine block of transient potassium current. J. Gen. Physiol. 80, 1–18 (1982).
Song, W.J. et al. Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A-type and attributable to coexpression of Kv4.2 and Kv4.1 subunits. J. Neurosci. 18, 3124–3137 (1998).
Kofuji, P., Davidson, N. & Lester, H.A. Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers. Proc. Natl. Acad. Sci. USA 92, 6542–6546 (1995).
Sheng, M., Liao, Y.J., Jan, Y.N. & Jan, L.Y. Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. Nature 365, 72–75 (1993).
Wang, H.S. et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel [see comments]. Science 282, 1890–1893 (1998).
Abbott, G.W. et al. MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell 104, 217–231 (2001).
Raz, A., Vaadia, E. & Bergman, H. Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine vervet model of parkinsonism. J. Neurosci. 20, 8559–8571 (2000).
Bergman, H., Wichmann, T., Karmon, B. & DeLong, M.R. The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J. Neurophysiol. 72, 507–520 (1994).
DeLong, M.R. & Wichmann, T. Deep brain stimulation for Parkinson's disease. Ann. Neurol. 49, 142–143 (2001).
Macica, C.M. & Kaczmarek, L.K. Casein kinase 2 determines the voltage dependence of the Kv3.1 channel in auditory neurons and transfected cells. J. Neurosci. 21, 1160–1168 (2001).
Murakoshi, H., Shi, G., Scannevin, R.H. & Trimmer, J.S. Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation. Mol. Pharmacol. 52, 821–828 (1997).
Rettig, J. et al. Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit. Nature 369, 289–294 (1994).
Surmeier, D.J., Bargas, J., Hemmings, H.C., Jr., Nairn, A.C. & Greengard, P. Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Neuron 14, 385–397 (1995).
Hamill, O.P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F.J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 391, 85–100 (1981).
Yan, Z. & Surmeier, D.J. Muscarinic (m2/m4) receptors reduce N- and P-type Ca2+ currents in rat neostriatal cholinergic interneurons through a fast, membrane-delimited, G-protein pathway. J. Neurosci. 16, 2592–2604 (1996).
Tkatch, T., Baranauskas, G. & Surmeier, D.J. Basal forebrain neurons adjacent to the globus pallidus co-express GABAergic and cholinergic marker mRNAs. Neuroreport 9, 1935–1939 (1998).
Rhodes, K.J. et al. Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes. J. Neurosci. 17, 8246–8258 (1997).
Acknowledgements
This work was supported by the National Institute of Neurological Disorders and Stroke (NS26473, NS34696 to D.J.S. and a National Parkinson Foundation (NPF) grant to T.T.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Baranauskas, G., Tkatch, T., Nagata, K. et al. Kv3.4 subunits enhance the repolarizing efficiency of Kv3.1 channels in fast-spiking neurons. Nat Neurosci 6, 258–266 (2003). https://doi.org/10.1038/nn1019
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn1019
This article is cited by
-
Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice
Neuroscience Bulletin (2021)
-
Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
Scientific Reports (2017)
-
Integration of electrophysiological recordings with single-cell RNA-seq data identifies neuronal subtypes
Nature Biotechnology (2016)
-
Genomics of alternative splicing: evolution, development and pathophysiology
Human Genetics (2014)
-
Optogenetic pharmacology for control of native neuronal signaling proteins
Nature Neuroscience (2013)