BIPHASIC EFFECT OF NICOTINE ON ACTION POTENTIAL REPOLARIZATION IN ELECTRICALLY DRIVEN GUINEA-PIG ATRIA

¹ Department of Pharmacology, University of Connecticut Health Center, McCook Hospital, Hartford, Connecticut

Intracellular action potentials (AP) were recorded from cells in the spontaneously beating sinoatrial node and electrically driven left atrial appendage of the guinea-pig heart bathed in Tyrode's solution at 30°C. Norepinephrine and small doses of nicotine (NIC) reduced spontaneous cycle length of sinoatrial node pacemaker cells and increased plateau amplitude and duration of left atrial AP. Propranolol antagonized the positive chronotropism of NIC and norepinephrine but had no effect on their ability to augment AP duration in left atrial cells. The increase in AP duration was blocked by dihydroergotamine. Acetylcholine and large doses of NIC increased spontaneous cycle length of sinoatrial node pacemaker cells and reduced AP duration in left atrial cells. Atropine prevented these actions of NIC and acetylcholine in the two atria. Since hexamethonium blocked the biphasic response of both atria to NIC, it appears that NIC acts indirectly by stimulation of adrenergic and cholinergic structures. Also, the sympathomimetic responses of left and right atria to NIC are mediated by an action of norepinephrine on qualitatively distinct receptor sites.

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