Calcium currents in chick embryo ventricular myocytes: Effects of dihydropyridine agonist Bay K 8644

Wattana Bamrungphol-Watanapa, University of Pennsylvania


Effects of 1,4-dihydropyridine Bay K 8644 on Ca channels were studied in isolated chick ventricular myocytes, using whole-cell patch clamp technique and tail current analysis. In control, two Ca channel types can be distinguished by the differences in kinetics, voltage dependence, DHP sensitivity, and divalent selectivity: the fast- and slowly-deactivating channels (equivalent to L- and T-type respectively). Deactivating time constants are 250 $\mu$s and 3 ms ($-$60 mV). In 500 nM Bay K 8644, pulse and tail current amplitudes are 1.8-3.8 times larger. SD channels are not affected. Tail current after SD has been subtracted is described by two exponential time constants ($-$60 mV), 400-500 $\mu$s and 2 ms (FBK and SBK). IV, g-V and h$\sb{\infty}$ curves are shifted by about $-$10 mV. Interestingly, inactivation is accelerated and becomes indistinguishable from SD inactivation ($\tau$ = 20-30 ms). SBK activates and inactivates with a slower kinetics than FBK. A novel method is introduced to test current dependence of inactivation. Cd$\sp{2+}$ is used to completely block pulse current, while inactivation time course is monitored by following tail current amplitude. This is possible because Cd$\sp{2+}$ block is voltage dependent, being greater at more positive potentials. In Bay K 8644, Cd$\sp{2+}$ does not change inactivation time course. Further, there is no parallelism between h$\sb{\infty}$ and IV curves. These evidence support the conclusion that Bay K-enhanced inactivation is not current dependent. The same approach was applied to unmodified FD channels. The conclusion from experiments using Cd$\sp{2+}$ and tail current analysis, from h$\sb{\infty}$ curve, and from comparing Ba and Ca currents, is that inactivation in unmodified channels is not calcium- or current-mediated. Finally, the possibility that Bay K 8644 acts by changing the affinity of Ca channels to permeant ions is tested. Specifically, Na$\sp+$ and Cs$\sp+$ permeability in 2-5 mM Ca$\sp{2+}$, at $-$80 mV, was studied and found unchanged by Bay K 8644. Therefore, under the limited test conditions, Bay K 8644 does not change Ca channel selectivity.

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Recommended Citation

Bamrungphol-Watanapa, Wattana, "Calcium currents in chick embryo ventricular myocytes: Effects of dihydropyridine agonist Bay K 8644" (1991). Dissertations available from ProQuest. AAI9200310.