Kcnma1 alternative splicing in mouse kidney: regulation during development and by dietary K⁺ intake

The pore-forming α subunit of the large conductance potassium (BK) channel is encoded by a single gene, KCNMA1. BK channel-mediated K⁺ secretion in the kidney is crucial for overall renal K⁺ homeostasis in both physiological and pathological conditions. BK channels achieve phenotypic diversity by various mechanisms, including substantial exon re-arrangements at seven major alternative splicing sites. However, KCNMA1 alternative splicing in the kidney has not been characterized. The current study aims to identify the major splice variants of mouse Kcnma1 in whole kidney and distal nephron segments. We designed primers that specifically cross exons within each alternative splice site of mouse Kcnma1 and performed real time RT-qPCR to quantify relative abundance of each splice variant. Our data suggest Kcnma1 splice variants within mouse kidney are less diverse than in the brain.During postnatal kidney development, most Kcnma1 splice variants at site 5 and the C-terminus increase in abundance over time. Within the kidney, the regulation of Kcnma1 alternative exon splicing within these two sites by dietary K⁺ loading is both site- and sex-specific. In microdissected distal tubules, the Kcnma1 alternative splicing profile, as well as its regulation by dietary K⁺, are distinctly different than in the whole kidney, suggesting segment and/or cell type specificity in Kcnma1 splicing events. Overall, our data provides evidence that Kcnma1 alternative splicing is regulated during postnatal development and may serve as an important adaptive mechanism to dietary K⁺ loading in mouse kidney.