Glucose- and arginine-induced insulin secretion by human pancreatic beta-cells: the role of HERG K+ channels in firing and release

The human ether-a-go-go-related genes (herg) are expressed in tissues other than heart and brain where the HERG K+ channels are known to regulate the repolarization of the heart action potential and the neuronal spike-frequen cy accommodation. We provide evidence that herg1 transcripts are present in human pancreatic islets that were used to study both insulin secretion and electrical activity with radioimmunoassay and single cell perforated patch -clamp techniques, respectively. Glucose- and arginine-induced islets insul in secretion data suggested a net increase of release under perfusion with antiarrhythmic drug known to selectively block HERG channels. Indeed we cou ld routinely isolate a K+ current that was recognized as biophysically and pharmacologically similar to the HERG current. An analysis of the glucose- and arginine-induced electrical activity (several applications during 30 mi n) in terms of firing frequency and putative insulin release was done in co ntrol and in the presence of selective blockers of HERG channels: the firin g frequency and the release increased by 32% and 77%, respectively. It is c oncluded that HERG channels have a crucial role in regulating insulin secre tion and firing of human beta -cells. This raises the possibility that some genetically characterized hyperinsulinemic diseases of unknown origin migh t involve mutations in the HERG channels.