Potassium secretion in rat distal colon during dietary potassium loading: role of pH regulated apical potassium channels

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); p<0.01) when surface cells were bathed in NaCl solution, and a similar difference in intracellular pH was observed when cells were bathed in Na2SO4 solution (7.67 (0.09) and 6.92 (0.05) respectively; p< 0.001). Ethylis opropylamiloride (EIPA; an inhibitor of Na+-H+ exchange; 1 mu M) 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 (Delta pH 0.50 (0.03)) rather than NaSO2SO4 (Delta pH 0.18 (0.02); p<0.05). In contrast, EIPA had no effect in cells from control animals. As assessed by patch clamp recording techniques, the activity of large conductance KC 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 mu M 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 Nac-He exchange, which may be a manifestation of the secondary hyperaldosteronism associated with this model of colonic K+ adaptation.