Ca2+-channel current and its modification by the dihydropyridine agonist BAY k 8644 in isolated smooth muscle cells.
The electrophysiological properties of single smooth muscle cells isolated from the longitudinal layer of the guinea-pig ileum were studied with the whole-cell patch-clamp technique. The finding of resting potentials between -45 and -50 mV and the occurrence of spontaneous electrical activity when K+ was the predominant intracellular cation indicated that the cells were not leaky or hyperpermeable. The existence of an inward Ca2+ current overlapping in time with an outward rectifying K+ current was demonstrated. The latter could be selectively blocked by replacing internal K+ with Cs+ and external Ca2+ with Ba2+. Depolarizations to potentials between -40 and +50 mV evoked time-dependent inward currents, with a maximum peak value between -20 and 0 mV. For depolarizations beyond +50 mV time-dependent outward currents appeared. These currents were inhibited by 0.1 mM CdCl2. The activation of the inward current showed a sigmoidal time course, and the rate of onset of the current increased at more positive potentials. Inactivation could be described by two exponentials. The threshold for activation was about -40 mV, and full activation was reached at 0 mV. Inactivation was complete near 0 mV, whereas the channels were fully available at -80 mV. The fully-activated Ca2+-channel current was strongly voltage dependent. The conductance decreased for potentials close to the reversal potential, and showed rectification for hyperpolarizing potentials. The Ca2+ agonist BAY k 8644 enhanced the Ca2+-channel current without a significant effect on its kinetics. The fully-activated current and the steady-state activation were enhanced in a rather voltage-independent way.
Droogmans
G
G
Callewaert
G
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000200:Action Potentials; D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides; D004095:Dihydropyridines; D006168:Guinea Pigs; D007082:Ileum; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials; D009130:Muscle, Smooth / Q000166:cytology*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors
D017609:Barium Compounds; D002712:Chlorides; D004095:Dihydropyridines; D007473:Ion Channels; D011725:Pyridines; C024986:barium chloride; D002586:Cesium; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; C028019:cesium chloride; D009543:Nifedipine