Role of a conserved glutamine in the function of voltage-gated Ca²⁺ channels revealed by a mutation in human CACNA1D.

ABSTRACT: Voltage-gated Ca_v Ca²⁺ channels play crucial roles in regulating gene transcription, neuronal excitability, and synaptic transmission. Natural or pathological variations in Ca_v channels have yielded rich insights into the molecular determinants controlling channel function. Here, we report the consequences of a natural, putatively disease-associated mutation in the CACNA1D gene encoding the pore-forming Ca_v1.3 α₁ subunit. The mutation causes a substitution of a glutamine residue that is highly conserved in the extracellular S1-S2 loop of domain II in all Ca_v channels with a histidine and was identified by whole-exome sequencing of an individual with moderate hearing impairment, developmental delay, and epilepsy. When

SUBMITTER: Garza-Lopez E 

PROVIDER: S-EPMC6139563 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature