Ionic mechanisms in pancreatic β cell signaling

Cell Mol Life Sci. 2014 Nov;71(21):4149-77. doi: 10.1007/s00018-014-1680-6. Epub 2014 Jul 23.

Abstract

The function and survival of pancreatic β 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 β 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 β 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 β 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 β cell at low levels. Ca(2+) influx through CaV1 channels, a major type of β cell CaV channels, causes the upstroke or depolarization phase of the action potential and regulates a wide range of β cell functions including the most elementary β cell function, insulin secretion. K(+) efflux mediated by KV2.1 delayed rectifier K(+) channels, a predominant form of β 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 β cell signaling. This review concisely discusses various ionic mechanisms in β cell signaling and highlights KATP channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials
  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Cell Membrane / metabolism
  • Exocytosis
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Ions / metabolism
  • Membrane Potentials
  • Potassium / metabolism
  • Potassium Channels / metabolism*
  • Signal Transduction*

Substances

  • Calcium Channels
  • Insulin
  • Ions
  • Potassium Channels
  • Adenosine Triphosphate
  • Potassium
  • Calcium