Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1975 Oct;251(3):775–790. doi: 10.1113/jphysiol.1975.sp011121

The interaction of pH and divalent cations at the neuromuscular junction.

E M Landau, D A Nachshen
PMCID: PMC1348416  PMID: 241848

Abstract

1. 1. The effects of acidic pH on transmitter release were studied at the frog neuromuscular junction, using intracellular recording techniques. 2. Acid pH reduced the amplitude of the end-plate potentials (e.p.p.s) and accelerated the frequency of the miniature e.p.p.s(m.e.p.p.s). 3. At pH 6-0 the m.e.p.p. frequency was on the average 2-5 times greater than at pH 7-4. This multiplication was independent of the divalent ion concentration of the medium over a large range. 4. Reduction of the e.p.p. amplitude at low pH was the result of a decrease in m, the number of quanta of transmitter liberated by the nerve impulse. 5. The effect of low pH on m was blocked by high concentrations of Mg2+ and by lower concentrations of Mn2+ ions. This occlusion was found even when the total concentration of divalents in the bathing solution was kept constant. 6. These results indicated that H+ and Mn2+ ions bind to an acidic site which regulates Ca-mediated release of acetylcholine (ACh). The acid dissociation constant (KH) was determined using both a kinetic and a surface charge model. The pKa of the site calculated from the kinetic model was 5-7, while a pKa of 3-6 was obtained from the surface charge model. 7. It is suggested that protonation of the acidic site mentioned above reduces evoked transmitter release by blocking the influx of Ca into the nerve terminal following the nerve action potential.

Full text

PDF
775

Selected References

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

  1. Alnaes E., Rahamimoff R. On the role of mitochondria in transmitter release from motor nerve terminals. J Physiol. 1975 Jun;248(2):285–306. doi: 10.1113/jphysiol.1975.sp010974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker P. F., Hodgkin A. L., Ridgway E. B. Depolarization and calcium entry in squid giant axons. J Physiol. 1971 Nov;218(3):709–755. doi: 10.1113/jphysiol.1971.sp009641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baker P. F., Meves H., Ridgway E. B. Effects of manganese and other agents on the calcium uptake that follows depolarization of squid axons. J Physiol. 1973 Jun;231(3):511–526. doi: 10.1113/jphysiol.1973.sp010246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colomo F., Rahamimoff R. Interaction between sodium and calcium ions in the process of transmitter release at the neuromuscular junction. J Physiol. 1968 Sep;198(1):203–218. doi: 10.1113/jphysiol.1968.sp008602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crawford A. C. The dependence of evoked transmitter release on external calcium ions at very low mean quantal contents. J Physiol. 1974 Jul;240(2):255–278. doi: 10.1113/jphysiol.1974.sp010609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. D'Arrigo J. S. Possible screening of surface charges on crayfish axons by polyvalent metal ions. J Physiol. 1973 May;231(1):117–128. doi: 10.1113/jphysiol.1973.sp010223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DEL CASTILLO J., KATZ B. Changes in end-plate activity produced by presynaptic polarization. J Physiol. 1954 Jun 28;124(3):586–604. doi: 10.1113/jphysiol.1954.sp005131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DEL CASTILLO J., NELSON T. E., Jr, SANCHEZ V. Mechanism of the increased acetylcholine sensitivity of skeletal muscle in low pH solutions. J Cell Comp Physiol. 1962 Feb;59:35–44. doi: 10.1002/jcp.1030590105. [DOI] [PubMed] [Google Scholar]
  9. Dodge F. A., Jr, Rahamimoff R. Co-operative action a calcium ions in transmitter release at the neuromuscular junction. J Physiol. 1967 Nov;193(2):419–432. doi: 10.1113/jphysiol.1967.sp008367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hagiwara S., Takahashi K. Surface density of calcium ions and calcium spikes in the barnacle muscle fiber membrane. J Gen Physiol. 1967 Jan;50(3):583–601. doi: 10.1085/jgp.50.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hermansen L., Osnes J. B. Blood and muscle pH after maximal exercise in man. J Appl Physiol. 1972 Mar;32(3):304–308. doi: 10.1152/jappl.1972.32.3.304. [DOI] [PubMed] [Google Scholar]
  12. Hubbard J. I., Jones S. F., Landau E. M. On the mechanism by which calcium and magnesium affect the release of transmitter by nerve impulses. J Physiol. 1968 May;196(1):75–86. doi: 10.1113/jphysiol.1968.sp008495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hubbard J. I., Jones S. F., Landau E. M. On the mechanism by which calcium and magnesium affect the spontaneous release of transmitter from mammalian motor nerve terminals. J Physiol. 1968 Feb;194(2):355–380. doi: 10.1113/jphysiol.1968.sp008413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Izutsu K. T. Intracellular pH, H ion flux and H ion permeability coefficient in bullfrog toe muscle. J Physiol. 1972 Feb;221(1):15–27. doi: 10.1113/jphysiol.1972.sp009735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. JENKINSON D. H. The nature of the antagonism between calcium and magnesium ions at the neuromuscular junction. J Physiol. 1957 Oct 30;138(3):434–444. doi: 10.1113/jphysiol.1957.sp005860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Katz B., Miledi R. Tetrodotoxin and neuromuscular transmission. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):8–22. doi: 10.1098/rspb.1967.0010. [DOI] [PubMed] [Google Scholar]
  17. Katz B., Miledi R. The release of acetylcholine from nerve endings by graded electric pulses. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):23–38. doi: 10.1098/rspb.1967.0011. [DOI] [PubMed] [Google Scholar]
  18. Lehninger A. L. Mitochondria and calcium ion transport. Biochem J. 1970 Sep;119(2):129–138. doi: 10.1042/bj1190129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MARTIN A. R. A further study of the statistical composition on the end-plate potential. J Physiol. 1955 Oct 28;130(1):114–122. doi: 10.1113/jphysiol.1955.sp005397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McLaughlin S. G., Szabo G., Eisenman G. Divalent ions and the surface potential of charged phospholipid membranes. J Gen Physiol. 1971 Dec;58(6):667–687. doi: 10.1085/jgp.58.6.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Meiri U., Rahamimoff R. Activation of transmitter release by strontium and calcium ions at the neuromuscular junction. J Physiol. 1971 Jul;215(3):709–726. doi: 10.1113/jphysiol.1971.sp009493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meiri U., Rahamimoff R. Neuromuscular transmission: inhibition by manganese ions. Science. 1972 Apr 21;176(4032):308–309. doi: 10.1126/science.176.4032.308. [DOI] [PubMed] [Google Scholar]
  23. Muller R. U., Finkelstein A. The electrostatic basis of Mg++ inhibition of transmitter release. Proc Natl Acad Sci U S A. 1974 Mar;71(3):923–926. doi: 10.1073/pnas.71.3.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Paillard M. Direct intracellular pH measurement in rat and crab muscle. J Physiol. 1972 Jun;223(2):297–319. doi: 10.1113/jphysiol.1972.sp009848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rahamimoff R., Alnaes E. Inhibitory action of Ruthenium red on neuromuscular transmission. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3613–3616. doi: 10.1073/pnas.70.12.3613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thomas R. C. Intracellular pH of snail neurones measured with a new pH-sensitive glass mirco-electrode. J Physiol. 1974 Apr;238(1):159–180. doi: 10.1113/jphysiol.1974.sp010516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van der Kloot W., Kita H. The possible role of fixed membrane surface charges in acetylcholine release at the frog neuromuscular junction. J Membr Biol. 1973;14(4):365–382. doi: 10.1007/BF01868085. [DOI] [PubMed] [Google Scholar]
  28. van Breemen C., Farinas B. R., Casteels R., Gerba P., Wuytack F., Deth R. Factors controlling cytoplasmic Ca 2+ concentration. Philos Trans R Soc Lond B Biol Sci. 1973 Mar 15;265(867):57–71. doi: 10.1098/rstb.1973.0009. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES