Nicotinic and muscarinic synaptic transmission in canine intracardiac ganglion cells innervating the sinoatrial node

Abstract

Nicotinic and muscarinic mediated synaptic mechanisms were investigated in isolated, canine intracardiac ganglia taken from the right atrial fat pad. Using conventional intracellular microelectrode recording techniques on 216 neurons, fast and slow synaptic potentials were evoked by single or trains of stimulation of presynaptic fibers in interganglionic nerves. By varying the stimulus intensity, single or multiple fast excitatory postsynaptic potentials (f-EPSPs) were evoked, indicating the convergence of synaptic inputs on these cells. These f-EPSPs often reached the action potential threshold, were enhanced by the acetylcholinesterase inhibitor physostigmine and were blocked by the nicotinic antagonist hexamethonium. The f-EPSPs were accompanied by a decreased input resistance and had an extrapolated reversal potential of -7.1 mV, suggesting increased conductances to more than one cation. Repetitive presynaptic stimulation evoked slow excitatory postsynaptic potentials (s-EPSPs) in 41% of the cells while slow inhibitory postsynaptic potentials (s-IPSPs) or s-IPSPs followed by s-EPSPs were evoked in 19% of the cells. All slow potentials were abolished by atropine and low Ca2+/high Mg2+ solutions and enhanced by physostigmine. Hexamethonium and adrenergic receptor antagonists had no effects on s-EPSP and s-IPSP. The M1 receptor antagonist pirenzepine reversibly blocked the s-EPSP but not the s-IPSP. On the other hand, the M2 receptor blocker 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP) had no effects on the s-EPSP. These observations suggest that s-EPSPs and s-EPSPs are mediated by distinct muscarinic receptors. The amplitude of the s-EPSP and the depolarization evoked by the muscarinic agonist, bethanechol were accompanied by increased input resistance. These responses were decreased in amplitude by membrane hyperpolarization and either reversed polarity or declined to zero amplitude at about -80 mV, suggesting the inhibition of a potassium conductance.