Modulation of K+ conductance by intracellular pH in pancreatic beta-cells.
Measurements of the effects of NH3/NH4+ on glucose-induced electrical activity in beta-cells from microdissected mouse islets of Langerhans and on intracellular pH in single collagenase-isolated islets pre-loaded with a fluorescent pH probe were performed and are reported here. Application of NH3/NH4+ (15 mM) in the presence of glucose (11 mM) promptly hyperpolarized the beta-cell membrane, reduced input resistance by 60% and blocked electrical activity. These changes were paralleled by an increase in islet fluorescence indicative of a cytosolic pH increase. Removal of NH4Cl initially stimulated electrical activity, which returned to resting level with a time constant of 51 s. Concomitant with the removal of NH4Cl there was a drop in pHi followed by a slow return to resting level with a time constant of 83 s. The results suggest that the [Ca2+]-dependent K+ channel in the beta-cell membrane is activated by a rise in cytosolic pH.
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D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D011188:Potassium / Q000378:metabolism*
D007473:Ion Channels; D000643:Ammonium Chloride; D005947:Glucose; D011188:Potassium