Human colonic crypt cells contain basolateral, intermediate conductance (23 pS), Ca²⁺-activated K⁺ (IK_Ca) channels, which play a role in chloride secretion (Sandle et al. 1994). Aldosterone (ALDO) has a protein kinase C (PKC)-mediated, non-genomic inhibitory effect on these channels (Bowley & Sandle, 2001). Non-genomic effects of ALDO in non-epithelial cells involves stimulation of Na⁺-H⁺ exchange (Falkenstein et al. 2000). Our aim was to determine whether ALDO’s effect on human colonic IK_Ca channels involves Na⁺-H⁺ exchange, which is known to be stimulated by PKC.

With ethics committee approval and informed consent, multiple biopsies were obtained from the distal colon of patients undergoing colonoscopy, who were free of mucosal disease. Intact crypts were isolated by Ca²⁺ chelation (Sandle et al. 1994). Basolateral IK_Ca channel activity (P_o) was recorded in the cell-attached configuration (NaCl solution in the bath, KCl solution in the pipette, holding voltage -40 mV). As reported previously (Bowley & Sandle, 2001), P_o decreased from 0.593 ± 0.055 to 0.281 ± 0.066 (mean ± S.E.M.) 5 min after adding 1 nM ALDO (P < 0.0002, Student’s two-tailed paired t test, n = 11), and decreased further from 0.267 ± 0.050 to 0.142 ± 0.045 5 min after adding a further 9 nM ALDO (P < 0.008, n = 7). Pretreatment of crypts with 20 µM ethyl isopropyl amiloride (EIPA, a Na⁺-H⁺ exchange inhibitor) had no effect on basal P_o, but completely prevented the inhibitory effect of 1 nM ALDO after 5 min (0.522 ± 0.100 vs. 0.541 ± 0.106, n = 7), and the effect of a further 9 nM ALDO after 5 min (0.437 ± 0.133 vs. 0.461 ± 0.141, n = 5).

These results suggest that ALDO’s non-genomic inhibitory effect on basolateral IK_Ca channels in human colonic crypt cells reflects intracellular alkalinization secondary to stimulation of Na⁺-H⁺ exchange by PKC.

K.A.B. was supported by an MRC PhD studentship.