An inwardly rectifying K+ conductance closely resembling the human ether-a-
go-go-related gene (HERG) current was identified in single smooth muscle ce
lls 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 rap
idly and then declined slowly (inactivated) during the test pulse in a time
- and voltage-dependent fashion. The HERG K+ channel blockers E-4031 (1 mu
M), cisapride (1 mu M), and La3+ (100 mu M) strongly inhibited these curren
ts as did millimolar concentrations of Ba2+ Immunoflourescence staining wit
h anti-HERG antibody in single cells resulted in punctate staining at the s
arcolemma. At membrane potentials near the resting membrane potential (-50
to -70 mV), this K+ conductance did not inactivate completely In convention
al 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 KERG-like K
+ currents in gastrointestinal smooth muscle cells and suggest that HERG pl
ays an important role in modulating the resting membrane potential.