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Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels Moreno, Claudia M Dixon, Rose E Tajada Esteban, Sendoa Yuan, Can Opitz-Araya, Ximena Binder, Marc D Santana, Luis F 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. 2024-02-06T10:21:05Z 2024-02-06T10:21:05Z 2016 info:eu-repo/semantics/article info:eu-repo/semantics/draft Elife. 2016 May 17;5:e15744. https://uvadoc.uva.es/handle/10324/65791 10.7554/eLife.15744 eLife 5 2050-084X spa info:eu-repo/semantics/openAccess application/pdf https://uvadoc.uva.es/bitstream/10324/65791/3/Moreno%20et%20al.%20-%202016%20-%20Ca2%20entry%20into%20neurons%20is%20facilitated%20by%20cooperative%20gating%20of%20clustered%20Cav1.3%20channels.pdf.jpg Hispana TEXT http://rightsstatements.org/vocab/CNE/1.0/ UVaDOC. Repositorio Documental de la Universidad de Valladolid https://uvadoc.uva.es/handle/10324/65791