Complex effects on Ca_V2.1 channel gating caused by a CACNA1A variant associated with a severe neurodevelopmental disorder.

ABSTRACT: P/Q-type Ca²⁺ currents mediated by Ca_V2.1 channels are essential for active neurotransmitter release at neuromuscular junctions and many central synapses. Mutations in CACNA1A, the gene encoding the principal Ca_V2.1 α_1A subunit, cause a broad spectrum of neurological disorders. Typically, gain-of-function (GOF) mutations are associated with migraine and epilepsy while loss-of-function (LOF) mutations are causative for episodic and congenital ataxias. However, a cluster of severe Ca_V2.1 channelopathies have overlapping presentations which suggests that channel dysfunction in these disorders cannot always be defined bimodally as GOF or LOF. In particular, the R1667P mutation causes focal seizures, generalized hypotonia, dysarthria, conge

SUBMITTER: Grosso BJ 

PROVIDER: S-EPMC9163077 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature