Abstract
1. Manganese, at low concentrations (0·5-2·0 mM), blocks neuromuscular transmission in toads. Endplate potentials (e.p.ps) are reduced in amplitude but the amplitude of miniature endplate potentials (m.e.p.ps) is, if anything, increased.
2. The release of transmitter by an action potential is reduced in solutions containing Mn, but is still well described by the Poisson equation.
3. Log-log plots of e.p.p. quantal content (m) against [Ca] have a mean gradient of 3·73, and a model based on the co-operative action of four calcium ions in excitation-secretion coupling, and competitive inhibition by Mn, was constructed. The model, with its exponent of 4, is shown in fact to predict gradients of less than four for log-log plots of m against [Ca].
4. The assumption of competitive inhibition by Mn was supported by modified Lineweaver-Burk plots of m-¼ against 1/[Ca]. The mean dissociation constants for Ca and Mn were 1·3 mM and 0·15 mM respectively. From the model, an upper estimate of the density of calcium `receptor sites' of 30 per square micron of nerve terminal was obtained.
5. In contrast to its inhibitory effect on evoked release, Mn increases the spontaneous release of transmitter. It is suggested that Mn may increase m.e.p.p. frequency by releasing Ca from an intracellular store.
Full text
PDF![339](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/6e58051e393e/brjpharm00548-0159.png)
![340](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/3f7e56cae5a5/brjpharm00548-0160.png)
![341](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/e21846dc7ef6/brjpharm00548-0161.png)
![342](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/996a21f8884f/brjpharm00548-0162.png)
![343](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/eb68a4b08ede/brjpharm00548-0163.png)
![344](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/0f318422d57f/brjpharm00548-0164.png)
![345](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/ea176522c5ce/brjpharm00548-0165.png)
![346](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/02c5d1380965/brjpharm00548-0166.png)
![347](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/a56025c2d0d3/brjpharm00548-0167.png)
![348](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/c95d5ed5ec71/brjpharm00548-0168.png)
![349](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/68d19620ea8a/brjpharm00548-0169.png)
![350](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/bb19781073a7/brjpharm00548-0170.png)
![351](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/e4772ed796fd/brjpharm00548-0171.png)
![352](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e6/1776558/9ae820aa5f0b/brjpharm00548-0172.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Blioch Z. L., Glagoleva I. M., Liberman E. A., Nenashev V. A. A study of the mechanism of quantal transmitter release at a chemical synapse. J Physiol. 1968 Nov;199(1):11–35. doi: 10.1113/jphysiol.1968.sp008637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bülbring E., Tomita T. Effect of calcium, barium and manganese on the action of adrenaline in the smooth muscle of the guinea-pig taenia coli. Proc R Soc Lond B Biol Sci. 1969 Mar 11;172(1027):121–136. doi: 10.1098/rspb.1969.0015. [DOI] [PubMed] [Google Scholar]
- Coraboeuf E., Vassort G. Effets de la tétrodotoxine, du tétraéthylammonium et du manganèse sur l'activité du myocarde de rat et de cobaye. C R Acad Sci Hebd Seances Acad Sci D. 1967 Feb 20;264(8):1072–1075. [PubMed] [Google Scholar]
- DEL CASTILLO J., ENGBAEK L. The nature of the neuromuscular block produced by magnesium. J Physiol. 1954 May 28;124(2):370–384. doi: 10.1113/jphysiol.1954.sp005114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DEL CASTILLO J., KATZ B. Quantal components of the end-plate potential. J Physiol. 1954 Jun 28;124(3):560–573. doi: 10.1113/jphysiol.1954.sp005129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DEL CASTILLO J., KATZ B. The effect of magnesium on the activity of motor nerve endings. J Physiol. 1954 Jun 28;124(3):553–559. doi: 10.1113/jphysiol.1954.sp005128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeBassio W. A., Schnitzler R. M., Parsons R. L. Influence of lanthanum on transmitter release at the neuromuscular junction. J Neurobiol. 1971;2(3):263–278. doi: 10.1002/neu.480020307. [DOI] [PubMed] [Google Scholar]
- 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]
- Gage P. W., Quastel D. M. Competition between sodium and calcium ions in transmitter release at mammalian neuromuscular junctions. J Physiol. 1966 Jul;185(1):95–123. doi: 10.1113/jphysiol.1966.sp007974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Good N. E., Winget G. D., Winter W., Connolly T. N., Izawa S., Singh R. M. Hydrogen ion buffers for biological research. Biochemistry. 1966 Feb;5(2):467–477. doi: 10.1021/bi00866a011. [DOI] [PubMed] [Google Scholar]
- HUBBARD J. I. The effect of calcium and magnesium on the spontaneous release of transmitter from mammalian motor nerve endings. J Physiol. 1961 Dec;159:507–517. doi: 10.1113/jphysiol.1961.sp006824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hagiwara S., Nakajima S. Differences in Na and Ca spikes as examined by application of tetrodotoxin, procaine, and manganese ions. J Gen Physiol. 1966 Mar;49(4):793–806. doi: 10.1085/jgp.49.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hashimoto Y., Holman M. E. Effect of manganese ions on the electrical activity of mouse vas deferens. Aust J Exp Biol Med Sci. 1967 Oct;45(5):533–539. doi: 10.1038/icb.1967.52. [DOI] [PubMed] [Google Scholar]
- Heuser J., Miledi R. Effects of lanthanum ions on function and structure of frog neuromuscular junctions. Proc R Soc Lond B Biol Sci. 1971 Dec 14;179(1056):247–260. doi: 10.1098/rspb.1971.0096. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- KATZ B., MILEDI R. THE EFFECT OF CALCIUM ON ACETYLCHOLINE RELEASE FROM MOTOR NERVE TERMINALS. Proc R Soc Lond B Biol Sci. 1965 Feb 16;161:496–503. doi: 10.1098/rspb.1965.0017. [DOI] [PubMed] [Google Scholar]
- Kajimoto N., Kirpekar S. M. Effect of manganese and lanthanum on spontaneous release of acetylcholine at frog motor nerve terminals. Nat New Biol. 1972 Jan 5;235(53):29–30. doi: 10.1038/newbio235029a0. [DOI] [PubMed] [Google Scholar]
- Katz B., Miledi R. A study of synaptic transmission in the absence of nerve impulses. J Physiol. 1967 Sep;192(2):407–436. doi: 10.1113/jphysiol.1967.sp008307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz B., Miledi R. Further study of the role of calcium in synaptic transmission. J Physiol. 1970 May;207(3):789–801. doi: 10.1113/jphysiol.1970.sp009095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz B., Miledi R. Modification of transmitter release by electrical interference with motor nerve endings. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):1–7. doi: 10.1098/rspb.1967.0008. [DOI] [PubMed] [Google Scholar]
- Katz B., Miledi R. Spontaneous and evoked activity of motor nerve endings in calcium Ringer. J Physiol. 1969 Aug;203(3):689–706. doi: 10.1113/jphysiol.1969.sp008887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kirpekar S. M., Dixon W., Prat J. C. Inhibitory effect of manganese on norepinephrine release from the splenic nerves of cats. J Pharmacol Exp Ther. 1970 Jul;174(1):72–76. [PubMed] [Google Scholar]
- 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]