Calcium channels

Abstract

A key step in renal calcium reabsorption is dihydropyridine-sensitive calcium entry across the apical membrane of the distal tubule. Electrophysiologic studies have confirmed the existence of calcium channels that may mediate this pathway. Molecular studies of voltage-dependent calcium channels have revealed a surprising degree of heterogeneity. The pore-forming alpha 1 subunit is encoded by multiple genes, each directing the synthesis of several alternatively spliced transcripts whose products may in turn be posttranslationally cleaved to yield multiple differently-sized peptides. Further heterogeneity is afforded by the presence of accessory subunits, such as the beta subunit, which is also encoded by a multigene family. Site-directed mutagenesis studies of the alpha 1 subunit have begun to explore the molecular structure of the calcium pore. Molecular cloning of rat renal calcium channel transcripts has identified alpha 1 and beta subunit genes that are expressed in the distal tubule. Future studies will address the structure-function relationship of various physiologic properties associated with the channels expressed by these genes.