Modulation of gating of a metabolically regulated, ATP-dependent K+ channel by intracellular pH in B cells of the pancreatic islet.
Membrane-permeant weak acids and bases, when applied to the bath, modulate the resting membrane potential and the glucose-induced electrical activity of pancreatic B cells, as well as their insulin secretion. These substances alter the activity of a metabolite-regulated, ATP-sensitive K+ channel which underlies the B-cell resting potential. We now present several lines of evidence indicating that the channel may be directly gated by pHi. (1) The time course of K+(ATP) channel activity during exposure to and washout of NH4Cl under a variety of experimental conditions, including alteration of the electrochemical gradient for NH4Cl entry and inhibition of the Na+o/H+i exchanger, resembles the time course of pHi measured in other cell types that have been similarly treated. (2) Increasing pHo over the range 6.25-7.9 increases K+(ATP) channel activity in cell-attached patches where the cell surface exposed to the bath has been permeabilized to H+ by the application of the K+/H+ exchanger nigericin. (3) Increasing pHi over a similar range produces similar effects on K+(ATP) channels in inside-out excised patches exposed to small concentrations of ATPi. The physiological role of delta pHi in the metabolic gating of this channel remains to be explored.
Misler
S
S
Department of Medicine, Washington University, St. Louis, Missouri 63110.
Gillis
K
K
Tabcharani
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins; D004553:Electric Conductivity; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D007515:Islets of Langerhans / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials; D009550:Nigericin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D027961:Potassium-Hydrogen Antiporters; D051381:Rats
D002352:Carrier Proteins; D015221:Potassium Channels; D027961:Potassium-Hydrogen Antiporters; D000643:Ammonium Chloride; D000255:Adenosine Triphosphate; D009550:Nigericin