Lowering of pHi inhibits Ca2+-activated K+ channels in pancreatic B-cells.
Glucose-dependent periodic electrical activity of membranes of pancreatic islet cells mediates calcium uptake, which is important for glucose-induced insulin release. As yet there has been no direct evidence identifying the 'second messenger' which couples the uptake and metabolism of glucose to the change of membrane electrical activity. Recent evidence showing that intracellular acidification stimulates islet B-cell electrical activity in a glucose-like manner has suggested that protons produced metabolically may serve as messengers by blocking K+ channels and depolarizing the membrane. Thus protons have been suggested to inhibit the Ca2+-activated K+-conductance [GK(Ca)] which is thought to produce the 'pacemaker' current responsible for the rhythmic firing of plateau depolarizations and Ca2+ spikes. Although these conductance channels have been characterized at the single channel level in several tissues, little is known of their response to intracellular pH (ref. 19) and they have not yet been characterized in B-cells. We have, therefore, used the patch-clamp method to study identified rat B-cells and show here that the B-cell GK(Ca) channel is activated by membrane depolarization as well as by cytoplasmic Ca2+, while it is inhibited by acidification of the cytoplasmic membrane surface.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism*; D051381:Rats
D007473:Ion Channels; D011188:Potassium; D002118:Calcium