Modulation of conduction slowing in ischemic rabbit myocardium by calcium-channel activation and blockade.
Ventricular action potentials and longitudinal conduction times over short distances of epicardium were recorded in isolated rabbit hearts. Global ischemia produced a progressive decrease of resting membrane potential, depression of action potentials, and conduction slowing to approximately 50% of control values over 8 to 10 min. Verapamil (2 X 10(-6) M) markedly attenuated ischemia-induced conduction slowing in association with less depression of maximum upstroke velocity (Vmax) and slightly less change in resting membrane potential. In contrast, Bay K 8644 (10(-7) M), a calcium-channel agonist, exacerbated ischemia-induced conduction slowing and depression of Vmax but did not significantly affect resting membrane potential. Regression analysis of Vmax vs resting membrane potential and the square of conduction velocity vs Vmax demonstrated that verapamil and Bay K 8644 shifted these relationships in opposite directions. The results indicate that the calcium-channel activation state can modulate slowing of conduction during early ischemia. This is most likely due to alterations in calcium influx before and/or during ischemia. There appear to be three possible components to this effect: (1) a small alteration in the magnitude of ischemia-induced depolarization, (2) alterations of membrane responsiveness at depolarized values of resting membrane potential, and (3) alterations in "nonactive" components of conduction during ischemia, such as changes in excitability or cell-to-cell coupling.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003327:Coronary Disease / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D011817:Rabbits; D012044:Regression Analysis; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D002118:Calcium