Evidence for voltage-gated potassium channel beta-subunits with oxidoreductase motifs in human and rodent pancreatic beta cells

Voltage-gated K+ channel alpha subunits (K(V)alpha) have been previously id entified in pancreatic islet beta -cells where it has been suggested they h ave a role in membrane repolarization and insulin secretion. Here we report the cloning of the three mammalian KVP subunits, including splice variants of these subunits. from both human and rat pancreatic islets and from the rat insulinoma cell Line INS-1. Two of the splice variants, K(V)beta 1a and K(V)beta3, previously reported to be neuronal tissue specific, are express ed in islets and INS-1 cells. In addition, a splice variant of K(v)beta2 th at lacks two potential protein kinase C phosphorylation sites at the amino terminus is present. Immunoblot analysis suggests a high level of K(V)beta2 subunit protein in rat pancreatic islets and immunoprecipitation with anti -K(V)beta2 antibody pulls down a protein from INS-1 cells that reacts with anti-aldose reductase antibody. The KVP subunits, which are attached to the cytoplasmic face of the a subunits and are members of the aldose reductase superfamily of NADPH oxidoreductases, may have an as yet undetermined role in the regulation of insulin secretion by the intracellular redox potentia l. Finally, we suggest that a systematic nomenclature for KVP subunits firs t proposed by McCormack et al. be adopted for this family of potassium chan nel subunits as it corresponds with the nomenclature used for their cognate K(V)alpha subunits.