Effects of cicletanine on whole-cell currents of single smooth muscle cells from the guinea-pig portal vein.
1. Smooth muscle cells of the guinea-pig portal vein were dispersed by enzymatic treatment and recordings of membrane currents were made in the whole-cell mode by the patch-clamp technique. The effects of extracellular application of cicletanine-hydrochloride on the whole-cell currents of isolated smooth muscle cells from the guinea-pig portal vein were studied in solutions containing a normal concentration of calcium (2.5 mM). 2. Cicletanine, 10 to 100 microM, reduced the voltage-dependent inward calcium current with an IC50 of 250 microM. These effects of cicletanine were reversible. 3. The action of cicletanine on calcium currents can be interpreted as a decrease of the availability of calcium channels but not by an alteration of the time course or voltage-dependency of inactivation. 4. The control calcium current was enhanced by application of Bay K 8644. On this enhanced inward current, cicletanine also exerted inhibitory effects which were not use-dependent. 5. Cicletanine, 1 to 100 microM, did not enhance outward potassium currents. 6. It is concluded that at least one component of the vasorelaxant effects of cicletanine is produced by inhibition of calcium currents.
Noack
T
T
Department of Physiology, Philipps University, Marburg, Germany.
Deitmer
P
P
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007473:Ion Channels; D011725:Pyridines; D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038068:cicletanine