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Farmer, Β. , Williams, E. , and Watanabe, A. M. (1983). Isolation of calcium tolerant myoctyes from adult rat hearts: Review of the literature and description of a method. LifeSci. 3 3 , 1-18. Frank, J. , Rich, T. , and Fireman, M. (1982). Calcium depletion in rabbit myocardium. Ultrastructure of the sarcolemma and correlation with the calcium paradox. Circ. Res. 5 1 , 117-130. , and Yamaguchi, K. (1981). Breakdown of cytoskeletal filaments selectively reduces Na and Ca spikes in cultured mammalian neurons.

Proc. 40, 2 6 1 8 - 2 6 2 4 . , and Shibata, E. F. (1985). Voltage clamp of isolated cardiac pacemaker cells from bullfrog sinus venosus: A quantitative analysis of potassium currents. J. Physiol (London) 368, 265-292. , and van Ginneken, A. (1985). A transient outward current in isolated cells from the crista terminalis of rabbit heart. J. Physiol. (London). 368, 2 4 3 - 2 6 4 . , and van Ginneken, A. (1986). Voltage clamp analysis of the f-current in isolated cells from the rabbit sinoatrial node: Its role in pacemaking.

Frequency-Dependent Block Thorough voltage-clamp investigations of the mechanisms of action of organic Ca-channel blockers have revealed that block of Ca current by all three classes of these compounds is strongly modulated by membrane potential. This phe­ nomenon is responsible for their frequency (use) -dependent block of contractile activity and Ca current in cardiac tissue. In all cases, inhibition of Ca current is facilitated by depolarization, caused by either increasing the frequency of stim­ ulation or, in the case of voltage-clamp studies, holding the membrane potential at depolarized levels.

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