Changes in pH alter the oscillatory pattern of glucose-induced electrical activity of mouse islet B cells, thereby supporting the hypothesis that changes in intracellular pH (pHi) resulting from glucose metabolism serve as a coupling factor between metabolic and cationic events. A decrease in pHi in the present of 11.1 mM glucose induces an increase in the duration of the active phase similar to that evoked by higher concentrations of glucose. Regulation of pHi appears to occur by Na:H and HCO3:Cl exchange in the plasma membrane, because inhibition by 0.1 mM amiloride and 0.5 mM 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS), respectively, induces constant spike activity in the presence of 11.1 mM glucose. If the pH coupling hypothesis is correct, then inhibition of the putative pH regulatory mechanisms and the subsequent decrease in pHi should elicit electrical activity in the presence of subthreshold glucose (less than 7.0 mM). Amiloride induced electrical activity (threshold) at 4.4 +/- 0.3 mM (mean +/- SEM) glucose. The threshold for DIDS was 5.4 +/- 0.2 glucose, whereas with glucose alone the threshold was achieved at 7.0 +/- 0.4 mM. Thus the generation of H+ by glucose may trigger changes in ionic conductances that induce the typical electrical response. Amiloride was found to elicit a secretory response at subthreshold glucose (4.2-7.0 mM) in perifused rat islets. This indicates that pH-induced changes in the ionic events in the B cells also play an important role in information transfer to the secretory complex.