Ca2+ entry into neurons is facilitated by cooperative gating of clustered Cav1.3 channels

Claudia M. Moreno, Rose Ellen Dickson, Sendoa Tajada, Can Yuan, Ximena Opitz-Araya, Marc D. Binder, Luis Fernando Santana

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 Ca2+ influx. CaV1.3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca2+ to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca2+ 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 Ca2+ signaling and electrical activity.

Original languageEnglish (US)
Article numbere15744
JournaleLife
Volume5
Issue numberMAY2016
DOIs
StatePublished - May 17 2016

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Calmodulin
Neurons
Optogenetics
Electric potential
Rats
Protein Isoforms
Chemical activation
Imaging techniques

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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Ca2+ entry into neurons is facilitated by cooperative gating of clustered Cav1.3 channels. / Moreno, Claudia M.; Dickson, Rose Ellen; Tajada, Sendoa; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D.; Santana, Luis Fernando.

In: eLife, Vol. 5, No. MAY2016, e15744, 17.05.2016.

Research output: Contribution to journalArticle

Moreno CM, Dickson RE, Tajada S, Yuan C, Opitz-Araya X, Binder MD et al. Ca2+ entry into neurons is facilitated by cooperative gating of clustered Cav1.3 channels. eLife. 2016 May 17;5(MAY2016). e15744. https://doi.org/10.7554/eLife.15744
Moreno, Claudia M. ; Dickson, Rose Ellen ; Tajada, Sendoa ; Yuan, Can ; Opitz-Araya, Ximena ; Binder, Marc D. ; Santana, Luis Fernando. / Ca2+ entry into neurons is facilitated by cooperative gating of clustered Cav1.3 channels. In: eLife. 2016 ; Vol. 5, No. MAY2016.
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