REGIONS OF BETA-2 AND BETA-4 RESPONSIBLE FOR DIFFERENCES BETWEEN THE STEADY-STATE DOSE-RESPONSE RELATIONSHIPS OF THE ALPHA-3-BETA-2 AND ALPHA-3-BETA-4 NEURONAL NICOTINIC RECEPTORS

被引：50

作者：

COHEN, BN

FIGL, A

QUICK, MW

LABARCA, C

DAVIDSON, N

LESTER, HA

机构：

[1] CALTECH,DIV BIOL,PASADENA,CA 91125

[2] UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521

[3] CALTECH,DIV CHEM & CHEM ENGN,PASADENA,CA 91125

来源：

JOURNAL OF GENERAL PHYSIOLOGY | 1995年 / 105卷 / 06期

关键词：

D O I：

10.1085/jgp.105.6.745

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits to locate the regions that contribute to differences between the acetylcholine (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an EC(50) for ACh similar to 20-fold less than the EC(50) of the alpha 3 beta 4 receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the first 120 residues convert the EC(50) for ACh from one wild-type value to the other. Exchanging just beta 2:104-120 for the corresponding region of beta 4 shifts the EC(50) of ACh dose-response relationship in the expected direction but does not completely convert the EC(50) Of the dose-response relationship from one wild-type value to the other. However, substitutions in the beta 2:104-120 region do account for the relative sensitivity of the alpha 3 beta 2 receptor to cytisine, tetramethylammonium, and ACh. The expression of beta 4-1ike (strong) cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2-like values. The results suggest that amino acids within the first 120 residues of beta 2 and the corresponding region of beta 4 contribute to an agonist binding site that bridges the alpha and beta subunits in neuronal nicotinic receptors.

引用

页码：745 / 764

页数：20

共 27 条

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