AJP - Heart and Circulatory Physiology, Vol 248, Issue 2 291-H296, Copyright © 1985 by American Physiological Society
Phenothiazine suppression of transient depolarizations in rabbit ventricular cells
M. S. Kremers, J. L. Kenyon, K. Ito and J. L. Sutko
We have examined the effects of trifluperazine and fluphenazine on action
potentials and transient depolarizations of rabbit ventricular cells.
Isolated myocytes were prepared by perfusing rabbit hearts with low calcium
enzyme-containing solutions, and action potentials were stimulated at 1 Hz
and recorded using patch-type pipettes. In normal saline, 10 microM
trifluperazine or fluphenazine shifted the action potential plateau to more
negative potentials and increased the rate of phase 2 repolarization.
Transient diastolic depolarizations appeared in solutions containing 50 nM
isoproterenol plus 1 microM strophanthidin. These transient depolarizations
were abolished by the addition of 10 microM trifluperazine or fluphenazine.
In addition, spontaneous transient depolarizations were occasionally
observed, and these too were abolished by the phenothiazines. Because these
compounds are potent inhibitors of calmodulin, these data raise the
possibility that calcium-calmodulin-regulated processes are important in
the generation of arrhythmogenic transient depolarizations.
