Somatostatin peptides inhibit basolateral potassium channels in human colonic crypts.

Somatostatin is a powerful inhibitor of intestinal Cl- secretion. We used patch-clamp recording techniques to investigate the effects of somatostatin on low-conductance (23-pS) K+ channels in the basolateral membrane of human colonic crypts, which are an important component of the Cl- secretory process. Somatostatin (2 μM) elicited a >80% decrease in "spontaneous" K+ channel activity in cell-attached patches in nonstimulated crypts (50% inhibition =∼8 min), which was voltage-independent and was prevented by pretreating crypts for 18 h with pertussis toxin (200 ng/ml), implicating a G protein-dependent mechanism. In crypts stimulated with 100-200 μM dibutyryl cAMP, 2 μM somatostatin and its synthetic analog octreotide (2 μM) both produced similar degrees of K+ channel inhibition to that seen in nonstimulated crypts, which was also present under low-Cl- (5 mM) conditions. In addition, 2 μM somatostatin abolished the increase in K+ channel activity stimulated by 2 μM thapsigargin but had no effect on the thapsigargin-stimulated rise in intracellular Ca2+. These results indicate that somatostatin peptides inhibit 23-pS basolateral K+ channels in human colonic crypt cells via a G protein-dependent mechanism, which may result in loss of the channel's inherent Ca2+sensitivity.