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Comparison of the effects of several calcium antagonistic drugs on the electrical activity of guinea pig Purkinje fibers.

Abstract：

:The effects of several slow channel blockers were compared on the normal fast action potentials (APs) and the slow APs of guinea pig Purkinje fibers. In spontaneously-firing Purkinje fibers perfused with normal Tyrode solution, mesudipine (analog of nifedipine) at 10(-7) and 10(-6) M, had no significant effect on the fast AP parameters (at 5 X 10(-6) M, excitability was abolished due to depolarization to about -45 mV). Washout of the drug rapidly (within 3 min) repolarized the preparations and restored automatic activity. In order to determine the effect of the calcium antagonists on the slow APs, the fast Na+ channels were inactivated by partial depolarization (to about -45 mV) by perfusing with 20 mM K+-Tyrode solution and isoproterenol (10(-6) M), or histamine (10(-5) M) were used to induce slow APs upon stimulation. Verapamil (10(-6) M) and nifedipine (10(-7) M) completely blocked the slow APs. Mesudipine at 10(-8) and 4 X 10(-8) M depressed the Vmax, amplitude and duration of the slow APs and abolished excitability within 11 min at 10(-7) M. At 10(-7) M, mesudipine blocked the slow APs earlier (within 3 min) at higher stimulation frequency (from the usual drive rate of 0.5-1.5 Hz). Lowering the stimulation frequency to 0.1 Hz restored the slow APs; however, the mesudipine block was independent of the stimulating frequency after 20 min. The dose/response curve for the mesudipine effect was shifted to the right in high Ca2+ concentration (5.4 mM). Washout of mesudipine and nifedipine restored the slow APs within 15 min, whereas verapamil required about 1 h. The results indicate that mesudipine has potent Ca2+ slow channel blocking properties in Purkinje fibers. Mesudipine and nifedipine are about ten times more potent than verapamil. This effect is not mediated by beta-adrenergic receptor antagonism, because the histamine-induced slow APs were also blocked.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Molyvdas PA,Sperelakis N

doi

10.1016/0014-2999(83)90007-9

subject

Has Abstract

pub_date

1983-03-25 00:00:00

pages

205-14

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

0014-2999(83)90007-9

journal_volume

pub_type

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Comparison of the effects of several calcium antagonistic drugs on the electrical activity of guinea pig Purkinje fibers.