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Departments of 1 Physiology and 2 Medicine, University of Western Ontario, and 3 Lawson Research Institute, St. Joseph's Health Centre, London, Ontario, Canada N6A 5C1
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.
acetylcholine; caffeine; fura 2; patch clamp; contraction
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