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

• Published in: The FASEB journal Vol. 14; no. 15; p. 2601
• Main Authors: Rosati, B, Marchetti, P, Crociani, O, Lecchi, M, Lupi, R, Arcangeli, A, Olivotto, M, Wanke, E
• Format: Journal Article
• Language: English
• Published: United States 01.12.2000
• Subjects: Arginine - pharmacology; ATP-Binding Cassette Transporters; Benzimidazoles - pharmacology; Cation Transport Proteins; DNA-Binding Proteins; Electric Conductivity; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Glucose - pharmacology; Humans; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; KATP Channels; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channel Blockers; Potassium Channels - metabolism; Potassium Channels, Inwardly Rectifying; Potassium Channels, Voltage-Gated; Radioimmunoassay; Reproducibility of Results; Sulfanilamides - pharmacology; Tolbutamide - pharmacology; Trans-Activators; Transcriptional Regulator ERG
• ISSN: 0892-6638
• DOI: 10.1096/fj.00-0077com

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-frequency 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 insulin secretion data suggested a net increase of release under perfusion with antiarrhythmic drugs known to selectively block HERG channels. Indeed we could 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 min) in terms of firing frequency and putative insulin release was done in control and in the presence of selective blockers of HERG channels: the firing frequency and the release increased by 32% and 77%, respectively. It is concluded that HERG channels have a crucial role in regulating insulin secretion and firing of human beta-cells. This raises the possibility that some genetically characterized hyperinsulinemic diseases of unknown origin might involve mutations in the HERG channels.