1 The effects of raising or lowering [Ca(2+)](o) or [Mg(2+)](o) on potential changes evoked by
5-hydroxytryptamine (5-HT) and by the
nicotinic agonist, 1,1-dimethyl-4-phenyl piperazinium (
DMPP) have been investigated.2 Changes in membrane potential were measured at the
ganglion or in postganglionic axons by the
sucrose-gap technique. The ganglionic response to both
5-HT and
DMPP was a depolarization followed by an after-hyperpolarization (AH). AH decayed exponentially over most of its time course; the time constant of decay for
5-HT responses was 4.4 +/- 0.3 min (mean +/- s.e.mean, rate constant 0.23 min(-1)) and that for
DMPP responses was not significantly different, being 3.9 +/- 0.3 min (rate constant 0.26 min(-1)).3 Increasing [Ca(2+)](o) to 5.1 or 7.6 mM caused some hyperpolarization of the
ganglion, reduced the amplitude of depolarizations evoked by
5-HT by 29% and usually potentiated responses to
DMPP (average 12%). Ca-free solutions caused a depolarization of the
ganglion, increased the amplitude of depolarizations evoked by
5-HT by 23% and reduced that of depolarizations to
DMPP by 32%. [Mg(2+)](o) 12.7 and 25.4 mM caused depolarizations of the
ganglion and reduced the amplitude of depolarizations evoked by
5-HT by 34 and 84%, respectively, and those to
DMPP by 10 and 75%, respectively. Mg-free solutions or low [Mg(2+)](o) caused a slow depolarization of the
ganglion and reduced the amplitude of depolarizations to both
5-HT and
DMPP by approx. 20%. Ca/Mg-free solutions produced a slow depolarization of the
ganglion, increased the amplitude of depolarizations evoked by
5-HT by 78% and reduced those to
DMPP by 58%.4 Increasing [Ca(2+)](o) reduced the amplitude of AH evoked by
5-HT by 50% and increased that to
DMPP by 73%, while prolonging AH duration and increasing the time constant of decay. Ca-free solutions had complex effects on AH evoked by
5-HT, which were increased on average by 116%, and depressed AH evoked by
DMPP; in both cases there was a decrease in the time constant of decay. [Mg(2+)](o) 12.7 mM reduced the amplitude of AH evoked by
5-HT more than that evoked by
DMPP, and increased the rate of decline of the exponential phase. Low Mg solutions reduced in amplitude the AH evoked by
5-HT by 56% and the AH evoked by
DMPP by 38%. The time constant of decay was increased. Ca/Mg-free solutions reduced AH amplitude in both
5-HT and
DMPP responses. The effects on time constant are consistent with the generation of AH by an electrogenic
sodium pump, the
ATP-ase of which is Mg(2+)-dependent and inhibited by Ca(2+).5 Responses to
5-HT could be recorded from postganglionic axons and consisted of a rapid depolarization, sometimes followed by an AH whose time constant of decay was smaller than that of ganglionic responses. Full dose-response curves in control and test media could be obtained. In Ca/Mg-free solutions,
5-HT depolarizations were potentiated but no significant shift in the curve was observed.6 It is suggested that
divalent cations modulate the coupling between
5-HT receptor and
ion channel, an increase in [Ca(2+)](o) reducing the coupling or stabilizing the
ion channel in the closed conformation. Ca(2+) and Mg(2+) may compete for the same binding site. This mechanism does not appear to be involved at
nicotinic receptors and their related
ion channels.