A biophysical model of electrical activity in human ?-cells.

ABSTRACT: Electrical activity in pancreatic ?-cells plays a pivotal role in glucose-stimulated insulin secretion by coupling metabolism to calcium-triggered exocytosis. Mathematical models based on rodent data have helped in understanding the mechanisms underlying the electrophysiological patterns observed in laboratory animals. However, human ?-cells differ in several aspects, and in particular in their electrophysiological characteristics, from rodent ?-cells. Hence, from a clinical perspective and to obtain insight into the defects in insulin secretion relevant for diabetes mellitus, it is important to study human ?-cells. This work presents the first mathematical model of electrical activity based entirely on published ion channel characteristics of human ?-cells. The model reproduces satisfactorily a series of experimentally observed patterns in human ?-cells, such as spiking and rapid bursting electrical activity, and their response to a range of ion channel antagonists. The possibility of Human Ether-a-Go-Go-related- and leak channels as drug targets for diabetes treatment is discussed based on model results.

SUBMITTER: Pedersen MG 

PROVIDER: S-EPMC2980734 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other