The hypothesis that cocaine has Class I-type antiarrhythmic drug effects was tested in tissues isolated from rabbit heart with standard microelectrode methods. Propranolol (1 microM) was used to block beta-adrenergic effects. The actions of cocaine on cellular electrophysiology were concentration- and time-dependent and were reversible. In paced right atrial (RA) and right ventricular papillary (RVP) tissues, cocaine produced a profound prolongation of the effective refractory period (ERP) assessed by either premature stimulation or minimum pacing interval. ERP was increased up to eightfold in RA tissue and doubled in RVP tissue by 60 microM cocaine. This concentration of cocaine depressed action potential phase 0 depolarization 80% in RA tissue and 53% in RVP tissue but had no effect on resting membrane potentials. Automaticity was moderately depressed in sinus node (34% decrease in rate) but not in tricuspid valve cells. Phase 0 depolarization was not altered in these spontaneously active slow-response cells. Repolarization was depressed in RA, tricuspid valve, and sinus node cells leading to a twofold increase in action potential duration during exposure to cocaine. Evidence from the effects on cellular action potentials suggests that cocaine affects both fast Na+ channels and repolarizing K+ but not Ca2+ channels. We conclude that cocaine has Class I-type activity and the effects on ERP are extreme.

SUMMARY1. The action of Ca on membrane excitability and synaptic transmission at motoneurones of the isolated spinal cord of the frog has been studied.2. Impulse propagation along presynaptic fibres was unaffected by [Ca] in the range of 0-10 mm in the presence of 1 mM-Mg. 3. Motoneurone membrane excitability was within normal ranges when the cord was bathed in low or 0 Ca solutions containing 1 mM-Mg but was depressed in 5 or 10 mM-Ca solutions.4. Spontaneous miniature synaptic potentials were recorded in the presence of tetrodotoxin. The frequencies were reduced but not abolished in the absence of bath Ca, but were increased greater than twofold in 5 or 10 mM-Ca in comparison to those in normal Ringer solution (1 mM-Ca).5. Iontophoretic application of Ca both near to and remotely from the intracellular recording site (presumably in the soma) caused facilitation of elicited post-synaptic potentials.6. It is concluded that the action of Ca at these central synapses is identical to that described at the neuromuscular junction.

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