Mouse muscle denervation increases expression of an α7 nicotinic receptor with unusual pharmacology

Hiroshi Tsuneki, Ramiro Salas, John A. Dani

研究成果: ジャーナルへの寄稿総説査読

39 被引用数 (Scopus)

抄録

Neuronal nicotinic α7 subunits have been found in chick and rat skeletal muscle during development and denervation. In the present study, reverse transcriptase-polymerase chain reaction was used to detect α7 subunit mRNA in denervated mouse muscle. To determine whether the α7 subunit forms functional nicotinic acetylcholine receptors (nAChRs) in muscle, choline was used to induce a membrane depolarization because choline has been considered a specific agonist of α7-containing (α7*) nAChRs. We found, however, that choline (3-10 mM) also weakly activates muscle nAChRs. After inhibiting muscle nAChRs with a specific muscle nAChR inhibitor, α-conotoxin GI (αCTxGI), choline was used to activate the α7* nAChRs on muscle selectively. Four weeks after denervation, rapid application of choline (10 mM) elicited a substantial depolarization in the presence of αCTxGI (0.1 μM). This component of the depolarization was never present in denervated muscles obtained from mutant mice lacking the α7 subunit (i.e. α7-null mice). The depolarization component that is resistant to αCTxGI was antagonized by pancuronium (3-10 μM) and by a 4-oxystilbene derivative (F3, 0.1-0.5 μM) at concentrations considered highly specific for α7* nAChRs. Another selective α7 antagonist, methyllycaconitine (0.05-5 μM), did not strongly inhibit this choline-induced depolarization. Furthermore, the choline-sensitive nAChRs showed little desensitization over 10 s of application with choline (10-30 mM). These results indicate that functional α7* nAChRs are significantly present on denervated muscle, and that these receptors display unusual functional and pharmacological characteristics.

本文言語英語
ページ(範囲)169-179
ページ数11
ジャーナルJournal of Physiology
547
1
DOI
出版ステータス出版済み - 2003/02/15

ASJC Scopus 主題領域

  • 生理学

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