Topic: Cav1.4

Ribbon synapses in the retina provide sustained glutamatergic transmitter release that is controlled by Cav1.4 L-type calcium channels in photoreceptors. In bipolar cells the voltage-gated calcium channels (VGCC) responsible for release are less conclusive. We therefore addressed the VGCCs expressed in mouse rod bipolar cells (RBC). We enriched RBCs by FACS-sorting and quantified mRNA expression levels of Cav1, Cav2 and auxiliary VGCC subunit isoforms, including selected splice variants. Transcript variants of candidate VGCC genes were confirmed in RT-PCR and through screening of RNAseq datase

Pathogenic variants in the CACNA1F gene, encoding retinal Cav1.4 L-type calcium channels can lead to a spectrum of altered functional channel activity, affecting the transmission of visual signals from photoreceptors to bipolar cells. Here, we investigated the effect of the Cav1.4 C-terminal truncation variant R1827X (RX) - lacking an intramolecular mechanism, necessary for continuous calcium influx- in mouse retinas and compared the phenotype to the apparent Cav1.4 gain-of-function variant I745T (IT). Whereas the significant decrease in the Cav1.4 protein can be attributed to a loss of photor