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. 1982 Apr;79(7):2406–2409. doi: 10.1073/pnas.79.7.2406

Triphenylmethylphosphonium is an ion channel ligand of the nicotinic acetylcholine receptor.

L Lauffer, F Hucho
PMCID: PMC346203  PMID: 6285383

Abstract

The lipophilic cation triphenylmethylphosphonium (Ph3MeP+), which is widely used as a sensor for membrane potential with cells, organelles, and membrane vesicles, is shown also to accumulate in membranes rich in nicotinic acetylcholine receptor in a voltage-independent way. Evidence is presented that Ph3MeP+ in this system is bound to a cation-binding site of the ion channel that is part of the acetylcholine receptor complex. Binding is stimulated by cholinergic effectors (Kd = 13 microM in the absence of carbamoylcholine; Kd = 1.5 microM in the presence of 10 microM carbamoylcholine), and this stimulation is blocked by alpha-bungarotoxin. Ph3MeP+ blocks efflux of 22Na from receptor-rich microsacs and appears to compete with the channel ligand phencyclidine for a common binding site. In contrast to the binding of other proven channel ligands, Ph3MeP+-binding is not affected by desensitization.

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Selected References

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

  1. Albuquerque E. X., Eldefrawi A. T., Eldefrawi M. E., Mansour N. A., Tsai M. C. Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor. Science. 1978 Feb 17;199(4330):788–790. doi: 10.1126/science.622570. [DOI] [PubMed] [Google Scholar]
  2. Albuquerque E. X., Tsai M. C., Aronstam R. S., Witkop B., Eldefrawi A. T., Eldefrawi M. E. Phencyclidine interactions with the ionic channel of the acetylcholine receptor and electrogenic membrane. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1224–1228. doi: 10.1073/pnas.77.2.1224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aronstam R. S., Eldefrawi A. T., Eldefrawi M. E. Similarities in the binding sites of the muscarinic receptor and the ionic channel of the nicotinic receptor. Biochem Pharmacol. 1980 May 1;29(9):1311–1314. doi: 10.1016/0006-2952(80)90292-0. [DOI] [PubMed] [Google Scholar]
  4. Aronstam R. S., Eldefrawi A. T., Pessah I. N., Daly J. W., Albuquerque E. X., Eldefrawi M. E. Regulation of [3H]perhydrohistrionicotoxin binding to Torpedo ocellata electroplax by effectors of the acetylcholine receptor. J Biol Chem. 1981 Mar 25;256(6):2843–2850. [PubMed] [Google Scholar]
  5. Eldefrawi M. E., Aronstam R. S., Bakry N. M., Eldefrawi A. T., Albuquerque E. X. Activation, inactivation, and desensitization of acetylcholine receptor channel complex detected by binding of perhydrohistrionicotoxin. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2309–2313. doi: 10.1073/pnas.77.4.2309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eldefrawi M. E., Eldefrawi A. T., Aronstam R. S., Maleque M. A., Warnick J. E., Albuquerque E. X. [3H]Phencyclidine: a probe for the ionic channel of the nicotinic receptor. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7458–7462. doi: 10.1073/pnas.77.12.7458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eldefrawi M. E., Eldefrawi A. T., Mansour N. A., Daly J. W., Witkop B., Albuquerque E. X. Acetylcholine receptor and ionic channel of Torpedo electroplax: binding of perhydrohistrionicotoxin to membrane and solubilized preparations. Biochemistry. 1978 Dec 12;17(25):5474–5484. doi: 10.1021/bi00618a023. [DOI] [PubMed] [Google Scholar]
  8. Elliot J., Raftery M. A. Interactions of perhydrohistrionicotoxin with postsynaptic membranes. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1347–1353. doi: 10.1016/s0006-291x(77)80127-7. [DOI] [PubMed] [Google Scholar]
  9. Elliott J., Raftery M. A. Binding of perhydrohistrionicotoxin to intact and detergent-solubilized membranes enriched in nicotinic acetylcholine receptor. Biochemistry. 1979 May 15;18(10):1868–1874. doi: 10.1021/bi00577a004. [DOI] [PubMed] [Google Scholar]
  10. Kaback H. R. Transport in isolated bacterial membrane vesicles. Methods Enzymol. 1974;31:698–709. doi: 10.1016/0076-6879(74)31075-0. [DOI] [PubMed] [Google Scholar]
  11. Komor E., Tanner W. The determination of the membrane ptoential of Chlorella vulgaris. Evidence for electrogenic sugar transport. Eur J Biochem. 1976 Nov 1;70(1):197–204. doi: 10.1111/j.1432-1033.1976.tb10970.x. [DOI] [PubMed] [Google Scholar]
  12. Oswald R., Changeux J. P. Ultraviolet light-induced labeling by noncompetitive blockers of the acetylcholine receptor from Torpedo marmorata. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3925–3929. doi: 10.1073/pnas.78.6.3925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ramos S., Grollman E. F., Lazo P. S., Dyer S. A., Habig W. H., Hardegree M. C., Kaback H. R., Kohn L. D. Effect of tetanus toxin on the accumulation of the permeant lipophilic cation tetraphenylphosphonium by guinea pig brain synaptosomes. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4783–4787. doi: 10.1073/pnas.76.10.4783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schiebler W., Hucho F. Membranes rich in acetylcholine receptor: characterization and reconstitution to excitable membranes from exogenous lipids. Eur J Biochem. 1978 Apr;85(1):55–63. doi: 10.1111/j.1432-1033.1978.tb12211.x. [DOI] [PubMed] [Google Scholar]
  15. Schuldiner S., Kaback H. R. Membrane potential and active transport in membrane vesicles from Escherichia coli. Biochemistry. 1975 Dec 16;14(25):5451–5461. doi: 10.1021/bi00696a011. [DOI] [PubMed] [Google Scholar]
  16. Sobel A., Heidmann T., Hofler J., Changeux J. P. Distinct protein components from Torpedo marmorata membranes carry the acetylcholine receptor site and the binding site for local anesthetics and histrionicotoxin. Proc Natl Acad Sci U S A. 1978 Jan;75(1):510–514. doi: 10.1073/pnas.75.1.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sugiyama H., Changeux J. P. Interconversion between different states of affinity for acetylcholine of the cholinergic receptor protein from Torpedo marmorata. Eur J Biochem. 1975 Jul 15;55(3):505–515. doi: 10.1111/j.1432-1033.1975.tb02188.x. [DOI] [PubMed] [Google Scholar]
  18. Tsai M. C., Mansour N. A., Eldefrawi A. T., Eldefrawi M. E., Albuquerque E. X. Mechanism of action of amantadine on neuromuscular transmission. Mol Pharmacol. 1978 Sep;14(5):787–803. [PubMed] [Google Scholar]
  19. Vacata V., Kotyk A., Sigler K. Membrane potentials in yeast cells measured by direct and indirect methods. Biochim Biophys Acta. 1981 Apr 22;643(1):265–268. doi: 10.1016/0005-2736(81)90241-8. [DOI] [PubMed] [Google Scholar]
  20. Zaritsky A., Macnab R. M. Effects of lipophilic cations on motility and other physiological properties of Bacillus subtilis. J Bacteriol. 1981 Sep;147(3):1054–1062. doi: 10.1128/jb.147.3.1054-1062.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

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