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  • Title: Calcium channel antagonist properties of Bay K 8644 in single guinea pig ventricular cells.
    Author: Hadley RW, Hume JR.
    Journal: Circ Res; 1988 Jan; 62(1):97-104. PubMed ID: 2446800.
    Abstract:
    The effects of Bay K 8644 on the high-threshold calcium channel was investigated by means of the whole-cell patch-clamp technique in single guinea pig ventricular myocytes. The goal of the experiments was to characterize the inhibitory effects of Bay K 8644 on the calcium channel, and identify the factors that influence the inhibition. Bay K 8644 was found to have strong calcium channel antagonist properties, which were both dose- and voltage-dependent. Channel block by Bay K 8644 had both a tonic and a use-dependent component. The stimulatory effect of the drug was found to have little obvious dependence on the holding potential. The accumulation of use-dependent block during trains of pulses was facilitated by faster rates of stimulation, longer pulse durations, and more positive holding potentials. Application of the drug induced the appearance of a second, slow component of calcium channel recovery. Both the time-constant and relative proportion of the slow component of recovery were found to be voltage-dependent. Bay K 8644 was also found to cause a hyperpolarizing shift of the inactivation curve for the calcium current, suggesting that it has strong interactions with the inactivated state of the calcium channel. Thus, Bay K 8644 has, along with its stimulatory effects, inhibitory effects that strongly resemble those of typical calcium channel antagonists.
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