Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1981 Jul;73(3):759–772. doi: 10.1111/j.1476-5381.1981.tb16813.x

Effects of divalent cations on responses of a sympathetic ganglion to 5-hydroxytryptamine and 1,1-dimethyl-4-phenyl piperazinium

HL Nash, DI Wallis
PMCID: PMC2071685  PMID: 6265020

Abstract

1 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.

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 [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 25.4 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 [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%.

4 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+.

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 [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.

Full text

PDF
759

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLACKMAN J. G., GINSBORG B. L., RAY C. On the quantal release of the transmitter at a sympathetic synapse. J Physiol. 1963 Jul;167:402–415. doi: 10.1113/jphysiol.1963.sp007158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett M. R., Florin T., Pettigrew A. G. The effect of calcium ions on the binomial statistic parameters that control acetylcholine release at preganglionic nerve terminals. J Physiol. 1976 Jun;257(3):597–620. doi: 10.1113/jphysiol.1976.sp011387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown D. A., Brownstein M. J., Scholfield C. N. Origin of the after-hyperpolarization that follows removal of depolarizing agents from the isolated superior cervical ganglion of the rat. Br J Pharmacol. 1972 Apr;44(4):651–671. doi: 10.1111/j.1476-5381.1972.tb07305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burgen A. S., Spero L. The effects of calcium and magnesium on the response of intestine smooth muscle to drugs. Br J Pharmacol. 1970 Nov;40(3):492–500. doi: 10.1111/j.1476-5381.1970.tb10630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FRANKENHAEUSER B., HODGKIN A. L. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. doi: 10.1113/jphysiol.1957.sp005808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Guerrero S., Riker W. K. Effects of some divalent cations on sympathetic ganglion function. J Pharmacol Exp Ther. 1973 Jul;186(1):152–159. [PubMed] [Google Scholar]
  7. Kuba K., Koketsu K. Synaptic events in sympathetic ganglia. Prog Neurobiol. 1978;11(2):77–169. doi: 10.1016/0301-0082(78)90010-2. [DOI] [PubMed] [Google Scholar]
  8. Lansdown M. J., Nash H. L., Preston P. R., Wallis D. I., Williams R. G. Antagonism of 5-hydroxytryptamine receptors by quipazine. Br J Pharmacol. 1980 Mar;68(3):525–532. doi: 10.1111/j.1476-5381.1980.tb14568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lees G. M., Wallis D. I. Hyperpolarization of rabbit superior cervical ganglion cells due to activity of an electrogenic sodium pump. Br J Pharmacol. 1974 Jan;50(1):79–93. doi: 10.1111/j.1476-5381.1974.tb09595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lièvremont M., Pascaud M. Etude de la sensibilité cholinergique à la jonction neuromusculaire, définition et rôle d'un opérant calcique. C R Acad Sci Hebd Seances Acad Sci D. 1972 Feb 28;274(9):1345–1348. [PubMed] [Google Scholar]
  11. McDougal D. B., Osborn L. A. Post-tetanic hyperpolarization, sodium-potassium-activated adenosine triphosphatase and high energy phosphate levels in garfish olfactory nerve. J Physiol. 1976 Mar;256(1):41–60. doi: 10.1113/jphysiol.1976.sp011310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rang H. P., Ritchie J. M. On the electrogenic sodium pump in mammalian non-myelinated nerve fibres and its activation by various external cations. J Physiol. 1968 May;196(1):183–221. doi: 10.1113/jphysiol.1968.sp008502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. TAKESHIGE C., VOLLE R. L. SIMILARITIES IN THE GANGLIONIC ACTIONS OF CALCIUM IONS AND ATROPINE. J Pharmacol Exp Ther. 1964 Aug;145:173–180. [PubMed] [Google Scholar]
  14. Takagi K., Takayanagi I., Liao C. S. The effect of calcium and magnesium ions on drug-receptor interactions. Eur J Pharmacol. 1972 Sep;19(3):330–342. doi: 10.1016/0014-2999(72)90099-4. [DOI] [PubMed] [Google Scholar]
  15. Taylor D. B. The role of inorganic ions in ion exchange processes at the cholinergic receptor of voluntary muscle. J Pharmacol Exp Ther. 1973 Sep;186(3):537–551. [PubMed] [Google Scholar]
  16. Tuttle R. R., Moran N. C. The effect of calcium depletion on the combination of agonists and competitive antagonists with alpha adrenergic and histaminergic receptors of rabbit aorta. J Pharmacol Exp Ther. 1969 Oct;169(2):255–263. [PubMed] [Google Scholar]
  17. Wallis D. I., Lees G. M., Kosterlitz H. W. Recording resting and action potentials by the sucrose-gap method. Comp Biochem Physiol C. 1975 Apr 1;50(2):199–216. [PubMed] [Google Scholar]
  18. Wallis D. I., Nash H. L. The action of methylated derivatives of 5-hydroxytryptamine at ganglionic receptors. Neuropharmacology. 1980 May;19(5):465–472. doi: 10.1016/0028-3908(80)90054-4. [DOI] [PubMed] [Google Scholar]
  19. Wallis D. I., North R. A. The action of 5-hydroxytryptamine on single neurones of the rabbit superior cervical ganglion. Neuropharmacology. 1978 Dec;17(12):1023–1028. doi: 10.1016/0028-3908(78)90028-x. [DOI] [PubMed] [Google Scholar]
  20. Wallis D. I., Woodward B. Membrane potential changes induced by 5-hydroxytryptamine in the rabbit superior cervical ganglion. Br J Pharmacol. 1975 Oct;55(2):199–212. doi: 10.1111/j.1476-5381.1975.tb07629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES