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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Weyrer C,Turecek J,Niday Z,Liu PW,Nanou E,Catterall WA,Bean BP,Regehr WGdoi
10.1016/j.celrep.2019.01.114subject
Has Abstractpub_date
2019-02-26 00:00:00pages
2289-2297.e3issue
9issn
2211-1247pii
S2211-1247(19)30151-2journal_volume
26pub_type
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