RT info:eu-repo/semantics/article
T1 Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels
A1 Moreno, Claudia M
A1 Dixon, Rose E
A1 Tajada, Sendoa
A1 Yuan, Can
A1 Opitz-Araya, Ximena
A1 Binder, Marc D
A1 Santana, Luis F
AB CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1.3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1.3S), but not the long (CaV1.3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca(2+) influx. CaV1.3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca(2+) to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca(2+) currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1.3S channels represents a mechanism for the regulation of Ca(2+) signaling and electrical activity.
YR 2016
FD 2016
LK https://uvadoc.uva.es/handle/10324/65791
UL https://uvadoc.uva.es/handle/10324/65791
LA spa
NO Elife. 2016 May 17;5:e15744.
DS UVaDOC
RD 16-jul-2024