Amiloride-sensitive regulation of intracellular pH in B-cells: activation by glucose.
Alterations in intracellular pH (pHi) generated by metabolism of glucose has been proposed to be a transduction device for controlling changes in K+ conductance in the plasma membrane of the B-cell leading to depolarization and cyclic variations in the membrane potential associated with spike activity. The influence of permeable weak acids or bases and amiloride inhibition of H+ extrusion by a Na:H exchanger on glucose-induced electrical activity has suggested that the electrical events are pH-sensitive. In order to document that these conditions alter pHi, we determined the influence of glucose, propionic acid, and NH4Cl, in the presence or absence of amiloride on pHi of rat islets using [14C] DMO. Glucose, 2.8 mmol/L decreased pHi by .09 unit compared to the absence of glucose (pHi = 7.08 +/- .01, M +/- SEM) and 16.7 mmol/L glucose reduced pHi by .19 unit. The glucose dose-related decrease in pHi yielded a half-maximal response at 4 mmol/L. The addition of 0.1 mmol/L amiloride had no influence on pHi without glucose and decreased pHi in the presence of 2.8 mmol/L glucose by .14 unit. The addition of 20 mmol/L propionic acid to 2.8 mmol/L glucose reduced pHi to 6.85 +/- .05, whereas 20 mmol/L NH4Cl increased pHi to 7.27 +/- .07. The addition of amiloride did not further lower the reduction in pHi elicited by 20 mmol/L propionic acid or 16.7 mmol/L glucose. These results suggest that the amiloride-sensitive Na:H exchanger plays a major role in regulation of pHi, but another modality for pHi regulation exists to compensate for inhibition of Na:H exchange under conditions of an acid load.
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002463:Cell Membrane Permeability; D004114:Dimethadione / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D008297:Male; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011422:Propionates; D000584:Amiloride; D004114:Dimethadione; D005947:Glucose; C029658:propionic acid