title: Electrical activity in pancreatic islet cells: The VRAC hypothesis.
abstract: A major aspect of stimulation of β-cell function by glucose is the induction of electrical activity. The ionic events that underlie β-cell electrical activity are understood in some detail. At sub-stimulatory glucose concentrations, the β-cell is electrically 'silent'. Increasing the glucose concentration to stimulatory levels results in a gradual depolarisation of the membrane potential to a threshold potential where 'spikes' or action potentials are generated. These action potentials represent the gating of voltage-sensitive Ca²(+) channels, leading to Ca²(+) entry into the cell, thus triggering the release of insulin. The stimulatory actions of glucose on the β-cell depend on the metabolism of the hexose. A major question concerns the molecular mechanism(s) whereby β-cell plasma membrane potential is regulated by changes in glucose metabolism in the cell. This article provides a brief summary of the evidence suggesting that, in addition to metabolically-regulated K(ATP) channels, β-cells are equipped with a volume-regulated anion channel that is activated by glucose concentrations within the range effective in modulating electrical activity and insulin release.
authors.affiliation: University of Manchester, UK. Len.Best@cmft.nhs.uk
authors.forename: Leonard
authors.initials: L
authors.lastname: Best
authors.forename: Peter D
authors.initials: PD
authors.lastname: Brown
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sener
authors.forename: Willy J
authors.initials: WJ
authors.lastname: Malaisse
mesh_terms: D000818:Animals; D048429:Cell Size; D055724:Electrophysiological Phenomena; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D015233:Models, Statistical; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D005947:Glucose