Monosynaptic muscarinic activation of K⁺ conductance underlies the slow inhibitory postsynaptic potential in sympathetic ganglia

Abstract

Slow muscarinic inhibition, which lasts seconds or longer, is probably an important modulator of synaptic interactions in the central and peripheral nervous systems. Neither the cellular location of muscarinic receptors nor the ionic mechanism underlying the inhibition is well understood. In parasympathetic neurones of the cardiac ganglion in the mudpuppy, activation of muscarinic receptors leads to an inhibitory postsynaptic potential (i.p.s.p.) produced by an increase in membrane conductance to K⁺ (ref. 1). At other sites, including sympathetic ganglia, however, the situation is less clear. In the 9th and 10th paravertebral sympathetic ganglia of the bullfrog stimulation of synaptic inputs to C neurones produces a slow muscarinic i.p.s.p.². From extracellular recordings, it was suggested³ that this slow i.p.s.p. is mediated through muscarinic excitation of an inhibitory, catecholamine-releasing interneurone. However, using similar methods, Weight et al.^4,5 reported that muscarinic receptors are located on C neurones themselves. Further controversy exists over the ionic basis of the i.p.s.p.; stimulation of an electrogenic ion pump^6,7 and reduction of membrane Na⁺ conductance⁸ have both been proposed but remain unsubstantiated. We now present evidence, from intracellular recordings, that acetyl-choline (ACh) produces a monosynaptic activation of muscarinic receptors located on sympathetic C neurones, and the i.p.s.p. is accompanied by an increase in membrane K⁺ conductance.