Voltage-dependent modulation of cardiac calcium channel current by optical isomers of Bay K 8644: implications for channel gating.
This study investigated the voltage-dependent actions of the stereoisomers of the 1,4-dihydropyridine Bay K 8644 on calcium channel currents in heart cells. Whole-cell currents were recorded from enzymatically dispersed ventricular myocytes using the patch-clamp technique. Both enantiomers of this compound modulate calcium channel current in a voltage-dependent manner. The most prominent effect of (+)-Bay K 8644 is an inhibition of calcium channel current, which is more pronounced when currents are measured from depolarized holding potentials. (-)-Bay K 8644 resembles the racemic compound; it enhances or inhibits currents depending on holding potential. The results of this study suggest that the dual activity of the racemic compound is not because of opposing actions of its component enantiomers.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D004594:Electrophysiology; D006168:Guinea Pigs; D007473:Ion Channels / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism
D007473:Ion Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium