Summary
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 pH i . (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 pH i measured in other cell types that have been similarly treated. (2) Increasing pH o 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 pH i over a similar range produces similar effects on K+(ATP) channels in inside-out excised patches exposed to small concentrations of ATP i . The physiological role of ΔpH i in the metabolic gating of this channel remains to be explored.
Similar content being viewed by others
References
Alberty, R.A., Smith, R.M., Bock, R.M. 1951. Apparent ionization constants of the adenosine phosphates and related compounds.J. Biol. Chem. 193:425–434
Ashcroft, F. 1988. Adenosine 5′-triphosphate-sensitive potassium channel.Annu. Rev. Neurosci. 11:97–118
Ashcroft, F.M., Kakei, M. 1987. Effects of external Mg2+ on ATP-sensitive K channels in isolated rat pancreatic B cells.J. Physiol. (London) 390:72P
Boron, W.F. 1985. Control of intracellular pH.In: The Kidney: Physiology and Pathophysiology. D.W. Seldin and G. Giebisch, editors. pp. 1417–1439. Raven, New York
Carroll, P.B., Li, M.X., Rojas, E., Atwater, I. 1988. The ATP-sensitive K+ channel in pancreatic B cells is inhibited in physiological bicarbonate buffer.FEBS Lett. 234:208–212
Cook, D.L., Hales, N. 1984. Intracellular ATP directly blocks K+ channels in pancreatic B cells.Nature (London) 311:271–273
Cook, D.L., Ikeuchi, M., Fujimoto, W.Y. 1984. Lowering of pH i inhibits Ca2+-activated K+ channels in pancreatic B cells.Nature (London) 311:269–271
Dunne, M.J., Illot, M.C., Petersen, O.H. 1987. Interaction of diazoxide, tolbutamide and ATP4− on nucleotide-dependent K+ channels in an insulin-secreting cell line.J. Membrane Biol. 99:215–224
Eddlestone, G.T., Beigelman, P.M. 1983. Pancreatic β cell electrical activity: The role of anions and control of pH.Am. J. Physiol. 244:C188-C197
Findlay, I., Dunne, M.J., Petersen, O.H. 1985. High-conductance K+ channel in pancreatic islet cells can be activated and inactivated by internal calcium.J. Membrane Biol. 83:169–175
Gillis, K., Misler, S. 1988. Effects of pH i on the activity of a metabolite regulated. ATP i -sensitive K+ channel in rat pancreatic islet cells.J. Gen. Physiol. 92:6–7a
Gillis, K., Tabcharani, J., Hammoud, A., Misler, S. 1988. Effects of ammonium chloride and sodium propionate on the activity of a metabolite regulated K+ channel in rat pancreatic islet and RIN insulinoma cells.Biophys. J. 53:550a
Misler, S., Falke, L.C., Gillis, K., McDaniel, M.L. 1986. A metabolite-regulated potassium channel in rat pancreatic B cells.Proc. Natl. Acad. Sci. USA 83:7119–7123
Misler, S., Gillis, K., Tabcharani, J., Falke, L. 1987. Gating and selectivity of a metabolite regulated K+ channel in rat pancreatic islet B cells.J. Gen. Physiol. 90:19a
Misler, S., Tabcharani, J., Gillis, K., Hammoud, A., Falke, L. 1988. Voltage gated single K+ and Ca2+ channels in rat pancreatic islet B cells.J. Gen. Physiol. 92:7a-8a
Pace, C.S. 1984a. Role of pH as a transduction device in triggering electrical and secretory responses in islet B cells.Fed. Proc. 43:2379–2384
Pace, C.S. 1984b. Amiloride and organic weak acids enhance the electrical response of B cells to glucose.Mol. Physiol. 6:339–348
Rorsman, P., Trube, G. 1986. Calcium and delayed potassium currents in mouse pancreatic β cell under voltage clamp conditions.J. Physiol. (London) 374:531–550
Rosario, L.M., Rojas, E. 1986a. Potassium channel selectivity in mouse pancreatic B cells.Am. J. Physiol. 250:C90-C94
Rosario, L.M., Rojas, E. 1986b. Modulation of K+ conductance by intracellular pH in pancreatic beta cells.FEBS Lett. 200:203–209
Smith, J.S., Pace, C.S. 1983. Modification of glucose induced insulin release by alteration of pH.Diabetes 32:61–66
Tabcharani, J.A., Misler, S. 1989. Ca2+ activated K+ channel in rat pancreatic islet B cells: Permeation gating and blockade by cations.Biochim. Biophys. Acta (in press)
Zuenkler, B.J., Trube, G., Ohno-Shosaku, T. 1988. Forskolin-induced block of delayed rectifier K+ channels in pancreatic β-cells is not mediated by cAMP.Pfluegers Arch. 411:613–619
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Misler, S., Gillis, K. & Tabcharani, J. Modulation of gating of a metabolically regulated, ATP-dependent K+ channel by intracellular pH in B cells of the pancreatic islet. J. Membrain Biol. 109, 135–143 (1989). https://doi.org/10.1007/BF01870852
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01870852