Effect of trimebutine on K+ current in rabbit ileal smooth muscle cells.
The effect of trimebutine on the K+ current in rabbit ileal smooth muscle cells was investigated using the whole-cell patch-clamp technique. Trimebutine (10 microM) inhibited an outward current consisting of a Ca(2+)-dependent K+ current (IKCa) and Ca(2+)-independent K+ current (IKv), elicited by stepping from -80 to -20 mV or more positive. Trimebutine reduced dose dependently the IKv amplitude with an IC50 of 7.6 microM and IKCa amplitude with an IC50 of 23.5 microM. The IKv inhibition was neither voltage- nor use-dependent. Trimebutine (1-100 microM) decreased the amplitude and discharge rate of spontaneous transient outward currents. Trimebutine (30 microM) produced a sustained membrane depolarization of about 10 mV accompanied by a decrease in membrane conductance. The results suggest that the excitatory effects of trimebutine on the gastrointestinal tract may be attributable to the inhibitory action on the K+ current.
Nagasaki
M
M
Department of Veterinary Science, Faculty of Agriculture, Gifu University, Japan.
Komori
S
S
Tamaki
H
H
Ohashi
H
H
D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects; D004594:Electrophysiology; D007082:Ileum / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014287:Trimebutine / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D014287:Trimebutine; D011188:Potassium; D002118:Calcium