Characterization and regulation of Ca2+-dependent K+ channels in human esophageal smooth muscle

We examined the properties of K+ channels in smooth muscle cells dissociate d from human esophagus using patch-clamp recording in the cell-attached con figuration. The predominant channel observed had a conductance of 224 +/- 4 pS, and current reversal was dependent on K+ concentration. Channel activi ty was voltage dependent and increased with elevation of intracellular free Ca2+ concentration ([Ca2+](i):), consistent with this being the large-cond uctance Ca2+ dependent K+ (Kc,) channel. ACh as well as caffeine caused tra nsient increases in Kc, channel activity, and the effects of ACh persisted in Ca2+-free solution, indicating that Ca2+ release from stores contributed to channel activation. Simultaneous patch clamp and fluorescence revealed that Kc, channel activity was well correlated with elevation of[Ca2+](i). T he functional role of Kc, channels in esophagus was studied by measuring AC h-induced contraction of strips of muscle. Tetraethylammonium and iberiotox in, blockers of Kc(a) channels, increased ACh-induced contraction, consiste nt with a role for K+ channels in limiting excitation and contraction. Thes e studies are the first to characterize Kc(a) channels and their regulation in human esophageal smooth muscle.