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 muM) inhibited an outward current consisting of a Ca2+-dependent K+ current (IK(Ca)) and Ca2+-independent K+ current (IK(v)), elicited by stepping from -80 to -20 mV or more positive. Trimebutine reduced dose dependently the IK(v) amplitude with an IC50 of 7.6 muM and IK(Ca) amplitude with an IC50 of 23.5 muM. The IK(v) inhibition was neither voltage- nor use-dependent. Trimebutine (1-100 muM) decreased the amplitude and discharge rate of spontaneous transient outward currents. Trimebutine (30 muM) 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.