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Effect of trimebutine on voltage‐activated calcium current in rabbit ileal smooth muscle cells
Author(s) -
Nagasaki Masaaki,
Komori Seiichi,
Ohashi Hidenori
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13823.x
Subject(s) - verapamil , biophysics , membrane potential , chemistry , patch clamp , voltage clamp , calcium , voltage dependent calcium channel , inhibitory postsynaptic potential , electrophysiology , pharmacology , endocrinology , medicine , biology
1 The effect of trimebutine on the voltage‐dependent inward Ca 2+ current was investigated by the whole‐cell voltage‐clamp technique in single smooth muscle cells from rabbit ileum. 2 Trimebutine (3–100 μ m ) reduced the Ca 2+ current in a concentration‐dependent manner. The inhibitory effect on the Ca 2+ current was also dependent on the holding potential. The Ca 2+ current after a low holding potential was inhibited to a greater extent than that after a high membrane potential: the IC 50 values were 7 μ m and 36 μ m at holding potentials of −40 mV and −60 mV, respectively. The Ca 2+ current elicited from a holding potential of −80 mV could not be reduced by as much as 50% of the control by trimebutine at concentrations as high as 100 μ m . 3 Trimebutine (30 μ m ) shifted the voltage‐dependent inactivation curve for the Ca 2+ current by 18 mV in the negative direction. The affinity of the drug for Ca 2+ channels was calculated to be 36 times higher in the inactivated state than in the closed‐available state. 4 Blockade of the Ca 2+ current by trimebutine, unlike verapamil, was not use‐dependent. 5 The results suggest that trimebutine inhibits the voltage‐dependent inward Ca 2+ current through a preferential binding to Ca 2+ channels in the inactivated state in the smooth muscle cell from rabbit ileum. The inhibitory effect of trimebutine on gastrointestinal motility is discussed in the light of the present findings.