EFFECTS OF DIVALENT CATIONS ON RESPONSES OF A SYMPATHETIC GANGLION TO 5‐HYDROXYTRYPTAMINE AND 1,1 ‐DIMETHYL‐4‐PHENYL PIPERAZINIUM
Authors: NASH H.L. , WALLIS D.I. 
Published: July 2012

The effects of raising or lowering [Ca2+]o or [Mg2+]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.

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).

Increasing [Ca2+]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%. [Mg2+]o 12.7 and 25.4mM 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 [Mg2+]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%.

Increasing [Ca2+]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. [Mg2+]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 Mg2+‐dependent and inhibited by Ca2+.

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.

It is suggested that divalent cations modulate the coupling between 5‐HT receptor and ion channel, an increase in [Ca2+]o reducing the coupling or stabilizing the ion channel in the closed conformation. Ca2+ and Mg2+ may compete for the same binding site. This mechanism does not appear to be involved at nicotinic receptors and their related ion channels.