Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventricular conduction in the dog

D. P. Zipes, J. C. Fischer

Research output: Contribution to journalArticle

213 Scopus citations


A slow ionic current carried by calcium, sodium, or both constitutes transmembrane ionic flow through the slow channel; such a current may be involved in normal action potentials of sinus and atrioventricular (AV) nodal cells. In this study, the authors investigated the effects of the slow channel inhibiting agents verapamil, D600, manganous chloride, and lanthanum chloride on sinus node automaticity and AV nodal conduction in open chest dogs treated with atropine (0.5 mg/kg) and propranolol (1.0 mg/kg). The arteries to the sinus node and the AV node were cannulated and perfused with agents that inhibit the slow current. These agents slowed sinus node discharge rate, depressed AV nodal conduction, and lengthened the effective and the functional AV nodal refractory period. Effects were dose related and reversed with time. His Purkinje conduction remained normal. Isoproterenol and epinephrine reversed the effects of slow channel inhibiting agents, but calcium, sodium, glucagon, and phenylephrine did not. Concentrations of propranolol which produced beta receptor blockade prevented isoproterenol induced reversal of the effects of slow channel inhibitors. It is concluded that agents which inhibit the slow channel directly depress sinus node discharge rate and AV nodal conduction, effects of slow channel inhibiting agents are not mediated through the activation of cholinergic discharge or inhibition of adrenergic discharge, and beta receptor stimulation reverses these effects.

Original languageEnglish (US)
Pages (from-to)184-192
Number of pages9
JournalCirculation research
Issue number2
StatePublished - Jan 1 1974


ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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