AGI Apr. 39/4

Hurley, Bernard R., Harold G. Preiksaitis, and Stephen M. Sims. Characterization and regulation of Ca21dependent K1 channels in human esophageal smooth muscle. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G843– G852, 1999.—We examined the properties of K1 channels in smooth muscle cells dissociated from human esophagus using patch-clamp recording in the cell-attached configuration. The predominant channel observed had a conductance of 224 6 4 pS, and current reversal was dependent on K1 concentration. Channel activity was voltage dependent and increased with elevation of intracellular free Ca21 concentration ([Ca]i), consistent with this being the large-conductance Ca21dependent K1 (KCa) channel. ACh as well as caffeine caused transient increases in KCa channel activity, and the effects of ACh persisted in Ca21-free solution, indicating that Ca21 release from stores contributed to channel activation. Simultaneous patch clamp and fluorescence revealed that KCa channel activity was well correlated with elevation of [Ca]i. The functional role of KCa channels in esophagus was studied by measuring ACh-induced contraction of strips of muscle. Tetraethylammonium and iberiotoxin, blockers of KCa channels, increased ACh-induced contraction, consistent with a role for K1 channels in limiting excitation and contraction. These studies are the first to characterize KCa channels and their regulation in human esophageal smooth muscle.