Electrical pacemaker mechanisms of pancreatic islet cells

Abstract

Glucose, the major physiological stimulus for insulin secretion, induces a periodic bursting pattern of Ca2+ action potentials that are thought to mediate the uptake of Ca2+ into the intracellular pool of free Ca2+, which controls the rate of insulin release. Evidence is reviewed that shows that the voltage-dependent Ca2+ spikes are driven by a slow, voltage-dependent plateau depolarization that may also be caused by Ca2+ influx. Current evidence suggests that this plateau conductance is periodically terminated in turn by a pacemaker current through membrane K+ channels that are activated by intracellular free Ca2+. The control of electrical activity by different modulators of insulin release may involve interactions with this system at several points, including changes of the sensitivity of K+ channels to intracellular Ca2+ and to changes of intracellular Ca2+ buffering capacity.