Abstract
IN skeletal muscle, L-type Ca2+ channels act as voltage sensors to control ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum1. It has recently been demonstrated that these ryanodine receptors generate a retrograde signal that modifies L-type Ca2+-channel activity2. Here we demonstrate a tight functional coupling between ryanodine receptors and L-type Ca2+ channel in neurons. In cerebellar granule cells, activation of the type-1 metabotropic glutamate receptor (mGluRl) induced a large, oscillating increase of the L-type Ba2+ current. Activation occurred independently of inositol 1,4,5-trisphosphate and classical protein kinases, but was mimicked by caffeine and blocked by ryanodine. The kinetics of this blockade were dependent on the frequency of Ba2+ current stimulation. Both mGluRl-and caffeine-induced increase in L-type Ca2+-channel activity persisted in inside-out membrane patches. In these excised patches, ryanodine suppressed both the mGluRl- and caffeine-activated L-type Ca2+ channels. These results demonstrate a novel mechanism for Ca2+-channel modulation in neurons.
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References
Rios, E. & Brum, G. Nature 325, 717–720 (1987).
Nakai, J. et al. Nature 380, 72–75 (1996).
Manzoni, O. et al. Mol. Pharmacol. 38, 1–6 (1990).
Chavis, P. et al. J. Neurosci. 15, 135–143 (1995).
Chavis, P., Fagni, L., Bockaert, J. & Lansman, J. B. Neuropharmacology 34, 929–937 (1995).
Chavis, P., Shinozaki, H., Bockaert, J. & Fagni, L. J. Neurosci. 14, 7067–7076 (1994).
Lambert, R. C. & Feltz, A. J. Neurosci. 15, 6014–6022 (1995).
Whitham, E. M., Challis, R. A. J. & Nahorski, S. R. Eur. J. Pharmacol. Mol. Sec. 206, 181–189 (1991).
De Waard, M., Seager, M., Feltz, A. & Couraud, F. Neuron 9, 497–503 (1992).
Hall, K. E., Browning, M. D., Dudek, E. M. & Macdonald, R. L. J. Neurosci. 15, 6069–6076 (1995).
Toullec, D. et al. J. Biol. Chem. 266, 15771–15781 (1991).
Fagni, L., Dumuis, A., Sebben, M. & Bockaert, J. Br. J. Pharmacol. 105, 973–979 (1992).
Irving, A. J., Collingride, G. L. & Shofield, J. G. J. Physiol. (Lod.) 456, 667–680 (1992).
Meszaros, L., Bak, J. & Chu, A. Nature 364, 76–79 (1993).
Linden, D. J., Smeyne, M. & Conno, J. A. Neuron 11, 1093–1100 (1993).
Conquet, F. et al. Nature 372, 237–243 (1994).
Linden, D. J. Neuron 12, 457–472 (1994).
Kohda, K., Inoue, T. & Mikoshiba, K. J. Neurophysiol. 74, 2184–2188 (1995).
Van-Vliet, B. J. et al. J. Neurochem. 52, 1229–1239 (1989).
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Chavis, P., Fagni, L., Lansman, J. et al. Functional coupling between ryanodine receptors and L-type calcium channels in neurons. Nature 382, 719–722 (1996). https://doi.org/10.1038/382719a0
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DOI: https://doi.org/10.1038/382719a0
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