Send to

Choose Destination
Elife. 2016 May 17;5. pii: e15744. doi: 10.7554/eLife.15744.

Ca(2+) entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels.

Author information

Department of Physiology and Membrane Biology, University of California, Davis, United States.
Department of Physiology and Biophysics, University of Washington, Seattle, United States.


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.


CaV1.3 channels; biophysics; calcium facilitation; hippocampal neurons; neuroscience; rat; structural biology

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center