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 a cetylcholine, ACh, which causes bradycardia. However, the responses to nerve stimulation are not well mimicked by exogenously applied ACh. T hese observations have led to the suggestion that there are subpopulat ions of muscarinic receptors on pacemaker cells and that during vagal stimulation neuronally released ACh caused slowing by suppressing inwa rd current flow during diastole. After the generation of action potent ials has been prevented by applying an organic calcium antagonist, vag al stimulation causes a hyperpolarization and an increase in membrane resistance: this observation suggests that the hyperpolarization resul ts from a supression of inward, presumably Na+, current flow. In this study we describe the effects of vagal stimulation on membrane potenti als recorded from arrested and beating hearts by using a computer mode l. The model of Noble & Noble (Proc. R. Soc. Lond. B 222, 295 (1984)) was modified to describe the shape of amphibian pacemaker action poten tials. A voltage-dependent Na conductance was included as well as two voltage-independent conductances, a background Na conductance and a ba ckground K conductance. Subsequently the hypothesis that the changes i n membrane potential recorded during vagal stimulation from arrested p reparations resulted from a reduction in Na conductance and this repre sented the sole action of vagally released ACh, was tested. If this we re so, the changes in membrane conductance that occur during vagal inh ibitory junction potentials recorded from arrested preparations should produce changes in pacemaker action potentials similar to those recor ded experimentally from beating preparations. This was found to be the case. Thus the analyses are consistent with the idea that vagal inhib ition of pacemaker cells results solely from a suppression of the two pacemaker sodium currents.