Abstract
Background: Chronic dietary K+ loading increases the abundance of large conductance (210 pS) apical K+ channels in surface cells of rat distal colon, resulting in enhanced K+ secretion in this epithelium. However, the factors involved in the regulation of these K+ channels are at present unclear.Aims: To evaluate the effect of dietary K+ loading on intracellular pH and its relation to large conductance apical K+ channel activity in surface cells of rat distal colon.Methods/Results: As assessed by fluorescent imaging, intracellular pH was higher in K+ loaded animals (7.48 (0.09)) than in controls (7.07 (0.04); p2SO4 solution (7.67 (0.09) and 6.92 (0.05) respectively; p+-H+ exchange; 1 μM) decreased intracellular pH when surface cells from K+ loaded animals were bathed in either solution, although the decrease was greater when the solution contained NaCl (ΔpH 0.50 (0.03)) rather than Na2SO4 (ΔpH 0.18 (0.02); p+ channels in excised inside-out membrane patches from distal colonic surface cells of K+ loaded animals increased twofold when the bath pH was raised from 7.40 to 7.60. As assessed by cell attached patches in distal colonic surface cells from K+ loaded animals, the addition of 1 μM EIPA decreased K+ channel activity by 50%, consistent with reversal of Na+-H+ exchange mediated intracellular alkalinisation.Conclusion: Intracellular alkalinisation stimulates pH sensitive large conductance apical K+ channels in rat distal colonic surface cells as part of the K+ secretory response to chronic dietary K+loading. Intracellular alkalinisation seems to reflect an increase in EIPA sensitive Na+-H+ exchange, which may be a manifestation of the secondary hyperaldosteronism associated with this model of colonic K+ adaptation.

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