Nuclear localization of calcium-activated BK channels in skate ampullary electroreceptors

Abstract

AbstractAmpullae of Lorenzini are sensory organs capable of detecting microvolt gradients in seawater. Electroreception involves interplay between voltage-dependent calcium channels CaV1.3 and big conductance calcium-activated potassium (BK) channels in apical membranes of receptor cells. Expression of BK (kcnma1) and CaV1.3 (cacna1d) channels in skate (Leucoraja erinacea) ampullary electroreceptors was studied by in situ confocal microscopy. BK and CaV1.3 channels colocalize in plasma membranes, ribbon synapses and kinocilia. BK channels additionally colocalize with chromatin and nuclear lamins in electroreceptor cells. Bioinformatic sequence analysis identified an alternatively spliced bipartite nuclear localization sequence (NLS) in kcnma1 (at site of mammalian STREX exon). Skate kcnma1 wild type cDNA transfected into HEK293 cells localized to the endoplasmic reticulum and nucleus. Mutations in the NLS (KR→AA or SVLS→AVLA) independently attenuated nuclear translocation from endoplasmic reticulum. BK channel localization may be controlled by splicing or phosphorylation to tune electroreception and modulate gene expression.