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). Ethylisopropylamiloride (EIPA; an inhibitor of Na⁺-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<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 K⁺ 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.