Characterisation of Alternative splicing of the Cav1.4 calcium channel gene

Abstract

CaV1.4, a member of the L-type family of voltage-gated calcium channels (LTCC), is predominantly expressed in the rod photoreceptor synapse and is etiological in congenital stationary night blindness type-2 (CSNB2). Using the transcript-scanning method, we identified nineteen different alternative splice variants of CaV1.4 in the human retina. Electrophysiological characterisation of the splice variants at the carboxyl cytosolic tail demonstrated modulations to activation, inactivation and recovery properties. Cassette exon 43* negatively shifted the I-V relationship, hyperpolarised shifted the window current, increased current density by four-fold, induced robust CDI, suppressed VDI and halved the rate of recovery from inactivation. Exon 45a-, derived from an alternative acceptor site, caused an intermediate slowing of the recovery rate. We demonstrated that the modulated activation and inactivation properties was a regulation targeted at the C-terminal modulator domain and also provided evidence that implicates a novel domain responsible for the post-inactivation recovery of the channel.