Beta-cell ion channels: keys to endodermal excitability.

Whereas pancreatic islet cells are not neurons, they are endodermally-derived specialized excitable cells that display many properties of neurons. Multiple ion channels in the pancreatic beta-cell regulate electrical excitability. Our focus for the last several years has been on the delayed rectifier (Kv) K+ channels, in an effort to define the individual roles of specific Kv channel genes in the overall regulation of insulin secretion. The many Kv channel genes, represented by more than 40 mammalian isoforms (termed Kv1 to Kv8), give rise to overlapping functions, primarily regulating repolarization of the plasma membrane. Experiments involving inhibition of Kv channel function have shown the important role Kv channels play in regulating beta-cell calcium oscillations in response to glucose stimulation. From our recent studies, we have concluded that although detectable mRNA for Kv1 family members is present in islets, Kv1 family channels are unlikely to play a significant role in the beta-cell, and we are now focusing on the roles of Kv2 and Kv3 channels.