The Role of CaV 2.1 Channel Facilitation in Synaptic Facilitation

Cell Reports
Christopher WeyrerWade G Regehr

Abstract

Activation of CaV2.1 voltage-gated calcium channels is facilitated by preceding calcium entry. Such self-modulatory facilitation is thought to contribute to synaptic facilitation. Using knockin mice with mutated CaV2.1 channels that do not facilitate (Ca IM-AA mice), we surprisingly found that, under conditions of physiological calcium and near-physiological temperatures, synaptic facilitation at hippocampal CA3 to CA1 synapses was not attenuated in Ca IM-AA mice and facilitation was paradoxically more prominent at two cerebellar synapses. Enhanced facilitation at these synapses is consistent with a decrease in initial calcium entry, suggested by an action-potential-evoked CaV2.1 current reduction in Purkinje cells from Ca IM-AA mice. In wild-type mice, CaV2.1 facilitation during high-frequency action potential trains was very small. Thus, for the synapses studied, facilitation of calcium entry through CaV2.1 channels makes surprisingly little contribution to synaptic facilitation under physiological conditions. Instead, CaV2.1 facilitation offsets CaV2.1 inactivation to produce remarkably stable calcium influx during high-frequency activation.

Citations

Mar 13, 2020·Nature Reviews. Neuroscience·Annette C Dolphin, Amy Lee
Jun 7, 2020·Journal of Molecular Neuroscience : MN·Yogesh Kumar Dhuriya, Divakar Sharma
Jun 2, 2020·Frontiers in Cellular Neuroscience·Agnes ThalhammerLorenzo A Cingolani
Aug 21, 2020·The Journal of Biological Chemistry·Nourdine ChakouriManu Ben-Johny
Nov 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·In Ha ChoMichael B Hoppa

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