Role of HERG-like K(+) currents in opossum esophageal circular smooth muscle.
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 microM), cisapride (1 microM), and La(3+) (100 microM) strongly inhibited these currents as did millimolar concentrations of Ba(2+). 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.
Akbarali
H I
HI
Center for Swallowing and Motility Disorders, Harvard Medical School, West Roxbury Veterans Affairs Medical Center, West Roxbury, Massachusetts 02132, USA. hakbarali@hms.harvard.edu
Thatte
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H
He
X D
XD
Giles
W R
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Goyal
R K
RK
D000818:Animals; D027682:Cation Transport Proteins; D020117:Cisapride / Q000494:pharmacology; D004947:Esophagus / Q000737:chemistry / Q000502:physiology*; D051638:Ether-A-Go-Go Potassium Channels; D005765:Gastrointestinal Agents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000737:chemistry / Q000502:physiology*; D009893:Opossums; D011188:Potassium / Q000493:pharmacokinetics*; D015221:Potassium Channels / Q000032:analysis / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D005765:Gastrointestinal Agents; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011188:Potassium; D020117:Cisapride