Characterization and regulation of Ca2+-dependent K+ channels in human esophageal smooth muscle.
We examined the properties of K+ 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 +/- 4 pS, and current reversal was dependent on K+ concentration. Channel activity was voltage dependent and increased with elevation of intracellular free Ca2+ concentration ([Ca2+]i), consistent with this being the large-conductance Ca2+-dependent K+ (KCa) channel. ACh as well as caffeine caused transient increases in KCa 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 KCa channel activity was well correlated with elevation of [Ca2+]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 K+ channels in limiting excitation and contraction. These studies are the first to characterize KCa channels and their regulation in human esophageal smooth muscle.
Hurley
B R
BR
Department of Physiology, University of Western Ontario, Canada.
Preiksaitis
H G
HG
Sims
S M
SM
D000109:Acetylcholine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D004947:Esophagus / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D015220:Calcium Channels; D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D002110:Caffeine; D019789:Tetraethylammonium; C064719:iberiotoxin; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium