Splicing of an automodulatory domain in Ca_v1.4 Ca²⁺ channels confers distinct regulation by calmodulin.

ABSTRACT: Ca²⁺ influx through Ca_v1.4 L-type Ca²⁺ channels supports the sustained release of glutamate from photoreceptor synaptic terminals in darkness, a process that is critical for vision. Consistent with this role, Ca_v1.4 exhibits weak Ca²⁺-dependent inactivation (CDI)-a negative feedback regulation mediated by Ca²⁺-bound calmodulin (CaM). CaM binds to a conserved IQ domain in the proximal C-terminal domain of Ca_v channels, but in Ca_v1.4, a C-terminal modulatory domain (CTM) disrupts interactions with CaM. Exon 47 encodes a portion of the CTM and is deleted in a Ca_v1.4 splice variant (Ca_v1.4Δex47) that is highly expressed in the human retina. Ca_v1.4Δex47 exhibits CDI and enhan

SUBMITTER: Williams B 

PROVIDER: S-EPMC6279360 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature