Modulation of in situ canine intrinsic cardiac neuronal activity by nicotinic, muscarinic, and beta-adrenergic agonists.

To investigate whether microvolumes (< or = 10 microliters) of nicotinic, muscarinic, and beta-adrenergic agonists can modify intrinsic cardiac neuronal activity, nicotine, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), bethanechol chloride, and isoproterenol were separately administered adjacent to spontaneously active in situ epicardial neurons in 15 anesthetized dogs. Neuronal activity generated by 46 of 63 neurons was modified by these neurochemicals, with about half of the neurons affected by more than one agent. In association with these neuronal responses, cardiodynamic responses were elicited in 17 instances. When cardiac augmentation was elicited, it persisted after the administration of atropine but not of timolol. After cardiac decentralization, 40% of previously active neurons were still modified by local application of chemicals; cardiodynamic responses were elicited in nine instances. The activity of six units was modified by isoproterenol after subsequent administration of hexamethonium. These data confirm that intrinsic cardiac neurons possess nicotinic and muscarinic receptors and demonstrate that some intrinsic cardiac neurons also possess beta-adrenergic receptors. Furthermore, these data demonstrate that intrinsic cardiac neurons with nicotinic, muscarinic, and beta-adrenergic receptors are involved in cardiac regulation.