Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Jan;76(1):531–535. doi: 10.1073/pnas.76.1.531

Tetraethylammonium: Voltage-dependent action on endplate conductance and inhibition of ligand binding to postsynaptic proteins

Michael Adler 1,*, Antonio C Oliveira 1, Mohyee E Eldefrawi 1, Amira T Eldefrawi 1, Edson X Albuquerque 1,†
PMCID: PMC382976  PMID: 284372

Abstract

Tetraethylammonium (Et4N+) ions depressed the amplitude and accelerated the decay rate of spontaneously occurring and nerve-evoked endplate currents (EPCs) in frog sartorius muscle. The relationship between peak EPC amplitude and membrane potential became nonlinear in the presence of 100 μM Et4N+, and with drug concentrations of 250 μM or greater the current-voltage relationship exhibited negative conductance in the hyperpolarized region. Et4N+ modified the exponential dependence of the EPC decay on membrane potential such that the decays between -150 and -50 mV were abbreviated and voltage independent but remained near control levels at more positive membrane potentials. The minimal effective concentration of Et4N+ for altering the EPC time course was 10, and maximal effects were attained with 100 μM. Little additional shortening in the EPC decay phase was detected on raising the drug concentration to 1000 μM. Acetylcholine noise analysis revealed a voltage-dependent reduction in the mean channel open time, which was comparable in magnitude to the shortening in the EPC decay, and a depression of single-channel conductance. In concomitant biochemical studies, Et4N+ was found to inhibit the binding of both [3H]acetylcholine and [3H]perhydrohistrionicotoxin to receptor-rich membranes from the electric organ of Torpedo ocellata with Ki values of 200 μM and 280 μM, respectively. These results suggest that Et4N+ interacts with both the acetylcholine receptor and its associated ionic channel. The voltage-dependent actions of Et4N+ are attributed to blockade of the ionic channel in closed as well as open conformation.

Keywords: acetylcholine receptor, endplate channel, acetylcholine noise, perhydrohistrionicotoxin, Torpedo electroplax

Full text

PDF
531

Images in this article

533Image
on p.533

Selected References

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

  1. Adams C. C., Celentano D. D. Standards for Maryland halfway house alcoholism programs. Md State Med J. 1975 Feb;24(2):61, 63-4. [PubMed] [Google Scholar]
  2. Adams P. R. Relaxation experiments using bath-applied suberyldicholine. J Physiol. 1977 Jun;268(2):271–289. doi: 10.1113/jphysiol.1977.sp011857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adler M., Albuquerque E. X. An analysis of the action of atropine and scopolamine on the end-plate current of frog sartorius muscle. J Pharmacol Exp Ther. 1976 Feb;196(2):360–372. [PubMed] [Google Scholar]
  4. Adler M., Albuquerque E. X., Lebeda F. J. Kinetic analysis of end plate currents altered by atropine and scopolamine. Mol Pharmacol. 1978 May;14(3):514–529. [PubMed] [Google Scholar]
  5. 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]
  6. Albuquerque E. X., Kuba K., Daly J. Effect of histrionicotoxin on the ionic conductance modulator of the cholinergic receptor: a quantitative analysis of the end-plate current. J Pharmacol Exp Ther. 1974 May;189(2):513–524. [PubMed] [Google Scholar]
  7. Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Armstrong C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. doi: 10.1085/jgp.58.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Armstrong C. M. Time course of TEA(+)-induced anomalous rectification in squid giant axons. J Gen Physiol. 1966 Nov;50(2):491–503. doi: 10.1085/jgp.50.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dionne V. E., Stevens C. F. Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. J Physiol. 1975 Oct;251(2):245–270. doi: 10.1113/jphysiol.1975.sp011090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eldefrawi A. T., Eldefrawi M. E., Albuquerque E. X., Oliveira A. C., Mansour N., Adler M., Daly J. W., Brown G. B., Burgermeister W., Witkop B. Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor. Proc Natl Acad Sci U S A. 1977 May;74(5):2172–2176. doi: 10.1073/pnas.74.5.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gage P. W., McBurney R. N., Van Helden D. Endplate currents are shortened by octanol: possible role of membrane lipid. Life Sci. 1974 Jun 1;14(11):2277–2283. doi: 10.1016/0024-3205(74)90109-x. [DOI] [PubMed] [Google Scholar]
  13. Gage P. W., McBurney R. N., Van Helden D. Octanol reduces end-plate channel lifetime. J Physiol. 1978 Jan;274:279–298. doi: 10.1113/jphysiol.1978.sp012147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KOKETSU K. Action of tetraethylammonium chloride on neuromuscular transmission in frogs. Am J Physiol. 1958 Apr;193(1):213–218. doi: 10.1152/ajplegacy.1958.193.1.213. [DOI] [PubMed] [Google Scholar]
  15. Katz B., Miledi R. The statistical nature of the acetycholine potential and its molecular components. J Physiol. 1972 Aug;224(3):665–699. doi: 10.1113/jphysiol.1972.sp009918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kordas M. The effect of membrane polarization on the time course of the end-plate current in frog sartorius muscle. J Physiol. 1969 Oct;204(2):493–502. doi: 10.1113/jphysiol.1969.sp008926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kordas M. The effect of procaine on neuromuscular transmission. J Physiol. 1970 Aug;209(3):689–699. doi: 10.1113/jphysiol.1970.sp009186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuba K., Albuquerque E. X., Daly J., Barnard E. A. A study of the irreversible cholinesterase inhibitor, diisopropylfluorophosphate, on time course of end-plate currents in frog sartorius muscle. J Pharmacol Exp Ther. 1974 May;189(2):499–512. [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Maeno T., Edwards C., Anraku M. Permeability of the endplate membrane activated by acetylcholine to some organic cations. J Neurobiol. 1977 Mar;8(2):173–184. doi: 10.1002/neu.480080208. [DOI] [PubMed] [Google Scholar]
  21. Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Magleby K. L., Stevens C. F. The effect of voltage on the time course of end-plate currents. J Physiol. 1972 May;223(1):151–171. doi: 10.1113/jphysiol.1972.sp009839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Masukawa L. M., Albuquerque E. X. Voltage- and time-dependent action of histrionicotoxin on the endplate current of the frog muscle. J Gen Physiol. 1978 Sep;72(3):351–367. doi: 10.1085/jgp.72.3.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ruff R. L. A quantitative analysis of local anaesthetic alteration of miniature end-plate currents and end-plate current fluctuations. J Physiol. 1977 Jan;264(1):89–124. doi: 10.1113/jphysiol.1977.sp011659. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES