Presynaptic interaction between vagal and sympathetic innervation in the heart: modulation of acetylcholine and...

It is generally accepted that there is a functional antagonism between the sympathetic and parasympathetic (vagal) effects on the heart. In this study guinea-pig right atria loaded either with [3H]noradrenaline or [3H]choline were used and the release of [3H]noradrenaline or [3H]acetylcholine in response to field stimulation was measured under conditions when the negative feedback modulation was excluded. Strong evidence was obtained for a one-sided interaction between the sympathetic and vagal nerves at the level of the prejunctional axon terminals that send the final chemical message to the heart muscle affecting heart rate and force. Acetylcholine released from the vagal nerve inhibited its own release and also decreased the release of noradrenaline from the sympathetic axon terminals through muscarinic receptor stimulation. But muscarinic receptors located on cholinergic axon terminals are different from those present on the noradrenergic axon terminals. There is a significant difference in the dissociation constants (Kd) of different antimuscarinic drugs: The Kd values of pancuronium on vagal and sympathetic axon terminals were 5.68 +/- 0.41 and 7.20 +/- 0.25, respectively. By contrast, noradrenaline released from the sympathetic nerves or exogenous noradrenaline were not able to modulate the release of acetylcholine from the cholinergic axon terminals even under condition when the negative feedback modulation of acetylcholine release was excluded. These findings indicate that vagal axon terminals are not equipped with alpha 2- or alpha 1-adrenoceptors. However, noradrenaline released from the sympathetic axon terminals was able to inhibit its own release via alpha 2-adrenoceptor stimulation.