Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels

摘要: CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it widely assumed that individual behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report results of super-resolution imaging, optogenetic, electrophysiological measurements refute this long-held view. We found short channel isoform (CaV1.3S), but not long (CaV1.3L), associates functional clusters two or more cooperatively, facilitating Ca(2+) influx. CaV1.3S are coupled via a C-terminus-to-C-terminus interaction requires binding incoming calmodulin (CaM) subsequent CaM pre-IQ domain channels. Physically-coupled facilitate currents as consequence their higher probabilities, leading increased firing rates rat hippocampal propose cooperative gating represents mechanism regulation signaling electrical activity.