Activation of Muscle Nicotinic Acetylcholine Receptor Channels by Nicotinic and Muscarinic Agonists

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1999 Dec 22

PMID 10602325

Citations 25

Authors

G Akk

A Auerbach

Affiliations

Soon will be listed here.

Abstract

1. The dose-response parameters of recombinant mouse adult neuromuscular acetylcholine receptor channels (nAChR) activated by carbamylcholine, nicotine, muscarine and oxotremorine were measured. Rate constants for agonist association and dissociation, and channel opening and closing, were estimated from single-channel kinetic analysis. 2. The dissociation equilibrium constants were (mM): ACh (0. 16)<oxotremorine M (0.6)<carbamylcholine (0.8)<nicotine (2.6). 3. The gating equilibrium constants (opening/closing) were: ACh (45)>carbamylcholine (5.1)>oxotremorine M (0.6)>nicotine (0. 5)>muscarine (0.15). 4. Rat neuronal alpha4beta2 nAChR can be activated by all of the agonists. However, detailed kinetic analysis was impossible because the recordings lacked clusters representing the activity of a single receptor complex. Thus, the number of channels in the patch was unknown and the activation rate constants could not be determined. 5. Considering both receptor affinity and agonist efficacy, muscarine and oxotremorine are significant agonists of muscle-type nAChR. The results are discussed in terms of structure-function relationships at the nAChR transmitter binding site.

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References

Wang H, Auerbach A, Bren N, Ohno K, Engel A, Sine S . Mutation in the M1 domain of the acetylcholine receptor alpha subunit decreases the rate of agonist dissociation. J Gen Physiol. 1997; 109(6):757-66. PMC: 2217038. DOI: 10.1085/jgp.109.6.757. View

Mulle C, Changeux J . A novel type of nicotinic receptor in the rat central nervous system characterized by patch-clamp techniques. J Neurosci. 1990; 10(1):169-75. PMC: 6570336. View

Qin F, Auerbach A, Sachs F . Estimating single-channel kinetic parameters from idealized patch-clamp data containing missed events. Biophys J. 1996; 70(1):264-80. PMC: 1224925. DOI: 10.1016/S0006-3495(96)79568-1. View

Akk G, Sine S, Auerbach A . Binding sites contribute unequally to the gating of mouse nicotinic alpha D200N acetylcholine receptors. J Physiol. 1996; 496 ( Pt 1):185-96. PMC: 1160835. DOI: 10.1113/jphysiol.1996.sp021676. View

Akk G, Zhou M, Auerbach A . A mutational analysis of the acetylcholine receptor channel transmitter binding site. Biophys J. 1999; 76(1 Pt 1):207-18. PMC: 1302512. DOI: 10.1016/S0006-3495(99)77190-0. View

Salamone F, Zhou M, Auerbach A . A re-examination of adult mouse nicotinic acetylcholine receptor channel activation kinetics. J Physiol. 1999; 516 ( Pt 2):315-30. PMC: 2269275. DOI: 10.1111/j.1469-7793.1999.0315v.x. View

Zhou M, Engel A, Auerbach A . Serum choline activates mutant acetylcholine receptors that cause slow channel congenital myasthenic syndromes. Proc Natl Acad Sci U S A. 1999; 96(18):10466-71. PMC: 17912. DOI: 10.1073/pnas.96.18.10466. View

Akk G, Auerbach A . Inorganic, monovalent cations compete with agonists for the transmitter binding site of nicotinic acetylcholine receptors. Biophys J. 1996; 70(6):2652-8. PMC: 1225244. DOI: 10.1016/S0006-3495(96)79834-X. View

Papke R, Boulter J, Patrick J, Heinemann S . Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Neuron. 1989; 3(5):589-96. DOI: 10.1016/0896-6273(89)90269-9. View

10.

Hong S, Chang C . Nicotinic actions of oxotremorine on murine skeletal muscle. Evidence against muscarinic modulation of acetylcholine release. Brain Res. 1990; 534(1-2):142-8. DOI: 10.1016/0006-8993(90)90124-t. View

11.

Shirvan M, Pollard H, Heldman E . Mixed nicotinic and muscarinic features of cholinergic receptor coupled to secretion in bovine chromaffin cells. Proc Natl Acad Sci U S A. 1991; 88(11):4860-4. PMC: 51766. DOI: 10.1073/pnas.88.11.4860. View

12.

Unwin N . Nicotinic acetylcholine receptor at 9 A resolution. J Mol Biol. 1993; 229(4):1101-24. DOI: 10.1006/jmbi.1993.1107. View

13.

Auerbach A . A statistical analysis of acetylcholine receptor activation in Xenopus myocytes: stepwise versus concerted models of gating. J Physiol. 1993; 461:339-78. PMC: 1175261. DOI: 10.1113/jphysiol.1993.sp019517. View

14.

Wess J . Mutational analysis of muscarinic acetylcholine receptors: structural basis of ligand/receptor/G protein interactions. Life Sci. 1993; 53(19):1447-63. DOI: 10.1016/0024-3205(93)90618-d. View

15.

Elgoyhen A, Johnson D, Boulter J, Vetter D, Heinemann S . Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell. 1994; 79(4):705-15. DOI: 10.1016/0092-8674(94)90555-x. View

16.

Unwin N . Acetylcholine receptor channel imaged in the open state. Nature. 1995; 373(6509):37-43. DOI: 10.1038/373037a0. View

17.

McGehee D, Role L . Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu Rev Physiol. 1995; 57:521-46. DOI: 10.1146/annurev.ph.57.030195.002513. View

18.

Sine S, Ohno K, Bouzat C, Auerbach A, Milone M, Pruitt J . Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity. Neuron. 1995; 15(1):229-39. DOI: 10.1016/0896-6273(95)90080-2. View

19.

Birdsall N, BURGEN A, Hulme E . The binding of agonists to brain muscarinic receptors. Mol Pharmacol. 1978; 14(5):723-36. View

20.

Sakmann B, Patlak J, Neher E . Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist. Nature. 1980; 286(5768):71-3. DOI: 10.1038/286071a0. View