The role of acetylcholine in synaptic transmission at parasympathetic ganglia

Abstract

It has usually been assumed, since the suggestion made by Dale (1933), that transmission at the parasympathetic ganglionic synapse is cholinergic, but proof of the validity of the assumption is difficult for two reasons. In the first place most parasympathetic ganglion cells are diffusely scattered throughout effector tissues and are not, as are sympathetic ganglion cells, congregated in anatomically recognizable ganglia; only three recognizable ganglia of the parasympathetic system are known, the ciliary, otic and spheno-palatine ganglia. In the second place, the postsynaptic, parasympathetic neurone is itself cholinergic, and when, as is usual, there is a diffuse scattering of ganglion cells, it is difficult to discover whether acetylcholine is released and stimulates at the ganglionic synapse or at the postganglionic-effector junction, or at both. Thus there is a volume of evidence, dating back to the classical experiments of Loewi (1921), that preganglionic, parasympathetic stmulation leads to the release of acetylcholine in such tissues as the heart and the intestine; but this acetylcholine could have been derived from either of the two junctional regions.Only in the work of Emmelin & Muren (1950) is evidence provided that acetylcholine is released at both synapses. They showed that in a perfused salivary gland, a ganglionic blocking drug (curare), given in doses sufficient to prevent salivary secretion on preganglionic stimulation, did not prevent the release of acetylcholine, although considerably reducing the total amount released; they concluded from these observations that the preganglionic nerve endings were releasing acetylcholine in spite of the ganglion block, inferring therefrom that transmission at the ganglionic synapse was cholinergic.The present experiments describe two ways in which the problem of para-* British Council Fellow.

The Action of Cardiac Glycosides on Autonomic Ganglia

“…The sensitization of the ganglion cells to the action of ACh produced by glycosides is very similar to the sensitization produced in denervated ganglia by the methonium compounds (Perry and Reinert, 1954b), which is probably associated with the transfer of potassium ions across the cell membrane. Thus, the failure of the glycosides to exert their sensitizing effect in the absence of external potassium may be significant, in that the action of ouabain may render the cell membrane more permeable to potassium ions, thus enhancing the effect of ACh.…”

“…The block of small doses of ACh produced by hexamethonium was interpreted by Perry and Talesnik (1953) as implying that these doses of ACh produced their action by stimulating the vagal ganglion cells and not the myocardium. In support of this contention they showed that hexamethonium did not exert any blocking action to the effect of stimulation of the post-ganglionic parasympathetic fibres supplying the pupil.…”

“…In the presence of hexamethonium, perfused in a concentration sufficient to block the ganglionic effects of ACh on the heart (Perry and Talesnik, 1953), ouabain no longer potentiates the action of ACh or of TMA. In Fig.…”

“…These results offered a means of testing whether any part of the action of glycosides on the heart was mediated through the intracardiac vagal ganglion cells, and this paper describes experiments carried out with this end in view. A preliminary account of some of these results has been published elsewhere (Perry and Reinert, 1954a).…”

“…Recently, Perry and Talesnik (1953) showed that the bradycardia produced by small doses of ACh in a perfused cat's heart could be prevented by small doses of ganglionic blocking drugs. They concluded that ACh, in such small doses, acted on the intracardiac ganglion cells of the vagus, the direct action of ACh on the myocardium being produced only when the dose was increased.…”