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1 Center for Swallowing and Motility Disorders, Harvard Medical School, West Roxbury Veterans Affairs Medical Center, West Roxbury, Massachusetts 02132; and 2 Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1
An inwardly
rectifying K+ conductance closely
resembling the human ether-a-go-go-related gene (HERG) current was
identified in single smooth muscle cells of opossum esophageal circular
muscle. When cells were voltage clamped at 0 mV, in isotonic
K+ solution (140 mM), step
hyperpolarizations to 
120 mV in 10-mV increments resulted in
large inward currents that activated rapidly and then declined slowly
(inactivated) during the test pulse in a time- and voltage- dependent
fashion. The HERG K+ channel
blockers E-4031 (1 µM), cisapride (1 µM), and
La3+ (100 µM) strongly inhibited
these currents as did millimolar concentrations of
Ba2+. Immunoflourescence staining
with anti-HERG antibody in single cells resulted in punctate staining
at the sarcolemma. At membrane potentials near the resting membrane
potential (50 to 70 mV), this
K+ conductance did not inactivate
completely. In conventional microelectrode recordings, both E-4031 and
cisapride depolarized tissue strips by 10 mV and also induced phasic
contractions. In combination, these results provide direct experimental
evidence for expression of HERG-like
K+ currents in gastrointestinal
smooth muscle cells and suggest that HERG plays an important role in
modulating the resting membrane potential.
human ether-a-go-go; resting membrane potential; cisapride; inward rectifier
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