Fr. Edwards et al., ANALYSIS OF THE EFFECTS OF VAGAL-STIMULATION ON THE SINUS VENOSUS OF THE TOAD, Philosophical transactions-Royal Society of London. Biological sciences, 341(1296), 1993, pp. 149-162
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.