Ionic mechanisms in pancreatic ß cell signaling.

ABSTRACT

The function and survival of pancreatic ß cells critically rely on complex electrical signaling systems composed of a series of ionic events, namely fluxes of K(+), Na(+), Ca(2+) and Cl(-) across the ß cell membranes. These electrical signaling systems not only sense events occurring in the extracellular space and intracellular milieu of pancreatic islet cells, but also control different ß cell activities, most notably glucose-stimulated insulin secretion. Three major ion fluxes including K(+) efflux through ATP-sensitive K(+) (KATP) channels, the voltage-gated Ca(2+) (CaV) channel-mediated Ca(2+) influx and K(+) efflux through voltage-gated K(+) (KV) channels operate in the ß cell. These ion fluxes set the resting membrane potential and the shape, rate and pattern of firing of action potentials under different metabolic conditions. The KATP channel-mediated K(+) efflux determines the resting membrane potential and keeps the excitability of the ß cell at low levels. Ca(2+) influx through CaV1 channels, a major type of ß cell CaV channels, causes the upstroke or depolarization phase of the action potential and regulates a wide range of ß cell functions including the most elementary ß cell function, insulin secretion. K(+) efflux mediated by KV2.1 delayed rectifier K(+) channels, a predominant form of ß cell KV channels, brings about the downstroke or repolarization phase of the action potential, which acts as a brake for insulin secretion owing to shutting down the CaV channel-mediated Ca(2+) entry. These three ion channel-mediated ion fluxes are the most important ionic events in ß cell signaling. This review concisely discusses various ionic mechanisms in ß cell signaling and highlights KATP channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes.