Both α- and β-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors

Charles W Luetje, Jim Patrick

Research output: Contribution to journalArticle

472 Citations (Scopus)

Abstract

A family of genes has been identified that encodes subunits of nicotinic acetylcholine receptors (nAChRs) and is expressed in the nervous system. Functional neuronal nAChRs can be expressed in Xenopus oocytes by injection of RNA encoding 1 of 2 different β-subunits (β2,β4) in pairwise combination with RNA encoding 1 of 3 different α-subunits (α2, α3, α4). We examined the sensitivity of these 6 different α-β-subunit combinations to the nicotinic agonists ACh, nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium (DMPP). Each subunit combination displayed a distinct pattern of sensitivity to these 4 agonists. The α2β2 combination was 5-fold more sensitive to nicotine than to acetylcholine, while the α3β2 combination was 17-fold less sensitive to nicotine than to ACh, and the α3β4 combination was equally sensitive to both nicotine and ACh. nAChRs composed of α2, α3, or α4 in combination with β2 were 14-100-fold less sensitive to cytisine than to ACh. In contrast, nAChRs composed of α2, α3, or α4 in combination with β4 were 3-17-fold more sensitive to cytisine than to ACh. The α2β2, α3β2, and α3β4 combinations were each equally sensitive to DMPP and ACh, while the α2β4, α4β2, and α4β4 combinations were 4-24-fold less sensitive to DMPP than to ACh. We also demonstrated that these differences are neither a consequence of variation in the relative amounts of RNA injected nor an artifact of oocyte expression. The oocyte system can accurately express ligand-gated ion channels because mouse muscle nAChRs expressed in oocytes display pharmacological properties similar to those reported for these receptors expressed on BC3H-1 cells. We conclude that both the α- and the β-subunits contribute to the pharmacological characteristics of neuronal nAChRs.

Original languageEnglish
Pages (from-to)837-845
Number of pages9
JournalJournal of Neuroscience
Volume11
Issue number3
StatePublished - Dec 1 1991
Externally publishedYes

Fingerprint

Nicotinic Receptors
Nicotine
Oocytes
RNA
Nicotinic Agonists
Pharmacology
Ligand-Gated Ion Channels
Xenopus
Artifacts
Nervous System
Acetylcholine
Muscles
Injections
Genes
cytisine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Both α- and β-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors. / Luetje, Charles W; Patrick, Jim.

In: Journal of Neuroscience, Vol. 11, No. 3, 01.12.1991, p. 837-845.

Research output: Contribution to journalArticle

@article{5fb366bc7b5d46d783ac7bd9ecda7576,
title = "Both α- and β-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors",
abstract = "A family of genes has been identified that encodes subunits of nicotinic acetylcholine receptors (nAChRs) and is expressed in the nervous system. Functional neuronal nAChRs can be expressed in Xenopus oocytes by injection of RNA encoding 1 of 2 different β-subunits (β2,β4) in pairwise combination with RNA encoding 1 of 3 different α-subunits (α2, α3, α4). We examined the sensitivity of these 6 different α-β-subunit combinations to the nicotinic agonists ACh, nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium (DMPP). Each subunit combination displayed a distinct pattern of sensitivity to these 4 agonists. The α2β2 combination was 5-fold more sensitive to nicotine than to acetylcholine, while the α3β2 combination was 17-fold less sensitive to nicotine than to ACh, and the α3β4 combination was equally sensitive to both nicotine and ACh. nAChRs composed of α2, α3, or α4 in combination with β2 were 14-100-fold less sensitive to cytisine than to ACh. In contrast, nAChRs composed of α2, α3, or α4 in combination with β4 were 3-17-fold more sensitive to cytisine than to ACh. The α2β2, α3β2, and α3β4 combinations were each equally sensitive to DMPP and ACh, while the α2β4, α4β2, and α4β4 combinations were 4-24-fold less sensitive to DMPP than to ACh. We also demonstrated that these differences are neither a consequence of variation in the relative amounts of RNA injected nor an artifact of oocyte expression. The oocyte system can accurately express ligand-gated ion channels because mouse muscle nAChRs expressed in oocytes display pharmacological properties similar to those reported for these receptors expressed on BC3H-1 cells. We conclude that both the α- and the β-subunits contribute to the pharmacological characteristics of neuronal nAChRs.",
author = "Luetje, {Charles W} and Jim Patrick",
year = "1991",
month = "12",
day = "1",
language = "English",
volume = "11",
pages = "837--845",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "3",

}

TY - JOUR

T1 - Both α- and β-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors

AU - Luetje, Charles W

AU - Patrick, Jim

PY - 1991/12/1

Y1 - 1991/12/1

N2 - A family of genes has been identified that encodes subunits of nicotinic acetylcholine receptors (nAChRs) and is expressed in the nervous system. Functional neuronal nAChRs can be expressed in Xenopus oocytes by injection of RNA encoding 1 of 2 different β-subunits (β2,β4) in pairwise combination with RNA encoding 1 of 3 different α-subunits (α2, α3, α4). We examined the sensitivity of these 6 different α-β-subunit combinations to the nicotinic agonists ACh, nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium (DMPP). Each subunit combination displayed a distinct pattern of sensitivity to these 4 agonists. The α2β2 combination was 5-fold more sensitive to nicotine than to acetylcholine, while the α3β2 combination was 17-fold less sensitive to nicotine than to ACh, and the α3β4 combination was equally sensitive to both nicotine and ACh. nAChRs composed of α2, α3, or α4 in combination with β2 were 14-100-fold less sensitive to cytisine than to ACh. In contrast, nAChRs composed of α2, α3, or α4 in combination with β4 were 3-17-fold more sensitive to cytisine than to ACh. The α2β2, α3β2, and α3β4 combinations were each equally sensitive to DMPP and ACh, while the α2β4, α4β2, and α4β4 combinations were 4-24-fold less sensitive to DMPP than to ACh. We also demonstrated that these differences are neither a consequence of variation in the relative amounts of RNA injected nor an artifact of oocyte expression. The oocyte system can accurately express ligand-gated ion channels because mouse muscle nAChRs expressed in oocytes display pharmacological properties similar to those reported for these receptors expressed on BC3H-1 cells. We conclude that both the α- and the β-subunits contribute to the pharmacological characteristics of neuronal nAChRs.

AB - A family of genes has been identified that encodes subunits of nicotinic acetylcholine receptors (nAChRs) and is expressed in the nervous system. Functional neuronal nAChRs can be expressed in Xenopus oocytes by injection of RNA encoding 1 of 2 different β-subunits (β2,β4) in pairwise combination with RNA encoding 1 of 3 different α-subunits (α2, α3, α4). We examined the sensitivity of these 6 different α-β-subunit combinations to the nicotinic agonists ACh, nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium (DMPP). Each subunit combination displayed a distinct pattern of sensitivity to these 4 agonists. The α2β2 combination was 5-fold more sensitive to nicotine than to acetylcholine, while the α3β2 combination was 17-fold less sensitive to nicotine than to ACh, and the α3β4 combination was equally sensitive to both nicotine and ACh. nAChRs composed of α2, α3, or α4 in combination with β2 were 14-100-fold less sensitive to cytisine than to ACh. In contrast, nAChRs composed of α2, α3, or α4 in combination with β4 were 3-17-fold more sensitive to cytisine than to ACh. The α2β2, α3β2, and α3β4 combinations were each equally sensitive to DMPP and ACh, while the α2β4, α4β2, and α4β4 combinations were 4-24-fold less sensitive to DMPP than to ACh. We also demonstrated that these differences are neither a consequence of variation in the relative amounts of RNA injected nor an artifact of oocyte expression. The oocyte system can accurately express ligand-gated ion channels because mouse muscle nAChRs expressed in oocytes display pharmacological properties similar to those reported for these receptors expressed on BC3H-1 cells. We conclude that both the α- and the β-subunits contribute to the pharmacological characteristics of neuronal nAChRs.

UR - http://www.scopus.com/inward/record.url?scp=0025934097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025934097&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 837

EP - 845

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 3

ER -