By Richard D. Nathan
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Extra resources for Cardiac Muscle: the Regulation of Excitation and Contraction
These results suggest that channels must open before the diarylalkylamine Ca-channel blockers can interact with a receptor and produce inhibition of Ca current. Ca-channel block by AQA39 or D600 that has developed during a train of stimuli is readily reversed by hyperpolarizing the membrane potential to - 9 0 mV for 90 sec (Pelzer et aL, 1982). This behavior was used to design a pulse protocol for further tests of whether activation of Ca channels is essential for block by D600 or AQA39 (Pelzer et aL, 1982).
An example of use-dependent effects of verapamil is illustrated in Fig. 8. Frequency-dependent block of current results from a drug-induced prolonga tion of the time required for the channels to recover from inactivation. Ca channels normally recover in a biexponential manner, the time constants of which are dependent on voltage. D600 (Pelzer et aL, 1982), verapamil (Kohlhardt and Mnich, 1978), nisoldipine (Sanguinetti and Kass, 1984a), nitrendipine (Lee and Tsien, 1983), and diltiazem (Uehara and Hume, 1984) all prolong this recovery process.
1984). Repolarization in cardiac muscle: An experimental and theoretical study using single cells from bullfrog atrium. Biophys. J. 45, 278a. Glitsch, H. , and Verdonck, F. (1985). The pacemaker current increases the intra cellular Na activity in isolated sheep cardiac Purkinje fibres. J. Physiol. (London) 366, 86p. , and Byerly, L. (1981). Calcium channel. Ann. Rev. Neurosci. 4 , 6 9 - 1 2 5 . , and Jaffe, L. A. (1979). Electrical properties of egg cell membranes. Ann Rev. Biophys. Bioeng. 8, 3 8 5 - 4 1 6 .
Cardiac Muscle: the Regulation of Excitation and Contraction by Richard D. Nathan