ANALYSIS OF THE EFFECTS OF VAGAL-STIMULATION ON THE SINUS VENOSUS OF THE TOAD

In amphibians and mammals, vagal stimulation leads to the release of acetylcholine, ACh, which causes bradycardia. However, the responses to nerve stimulation are not well mimicked by exogenously applied ACh. These observations have led to the suggestion that there are subpopulations of muscarinic receptors on pacemaker cells and that during vagal stimulation neuronally released ACh caused slowing by suppressing inward current flow during diastole. After the generation of action potentials has been prevented by applying an organic calcium antagonist, vagal stimulation causes a hyperpolarization and an increase in membrane resistance: this observation suggests that the hyperpolarization results from a supression of inward, presumably Na+, current flow. In this study we describe the effects of vagal stimulation on membrane potentials recorded from arrested and beating hearts by using a computer model. The model of Noble & Noble (Proc. R. Soc. Lond. B 222, 295 (1984)) was modified to describe the shape of amphibian pacemaker action potentials. A voltage-dependent Na conductance was included as well as two voltage-independent conductances, a background Na conductance and a background K conductance. Subsequently the hypothesis that the changes in membrane potential recorded during vagal stimulation from arrested preparations resulted from a reduction in Na conductance and this represented the sole action of vagally released ACh, was tested. If this were so, the changes in membrane conductance that occur during vagal inhibitory junction potentials recorded from arrested preparations should produce changes in pacemaker action potentials similar to those recorded experimentally from beating preparations. This was found to be the case. Thus the analyses are consistent with the idea that vagal inhibition of pacemaker cells results solely from a suppression of the two pacemaker sodium currents.