Acetylcholine receptor M3 domain: stereochemical and volume contribution to channel gating

Anna Paola Batocchi, Wang Hl, M Milone, K Ohno, Shen Xm, A Tsujino, Pietro Attilio Tonali, J Brengman, Engel Ag, Sine S.m.

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

By defining the functional defect in a congenital myasthenic syndrome (CMS), we show that the third transmembrane domain (M3) of the muscle acetylcholine receptor governs the speed and efficiency of gating of its channel. The clinical phenotype of this CMS results from the mutation V285I in M3 of the alpha subunit, which attenuates endplate currents, accelerates their decay and causes abnormally brief acetylcholine-induced single-channel currents. Kinetic analysis of engineered alpha V285I receptors demonstrated a predominant effect on channel gating, with abnormally slow opening and rapid closing rates. Analysis of site-directed mutations revealed stereochemical and volume-dependent contributions of alpha V285 to channel gating. Thus, we demonstrate a functional role for the M3 domain as a key component of the nicotinic acetylcholine receptor channel-gating mechanism
Lingua originaleEnglish
pagine (da-a)226-233
Numero di pagine8
RivistaNature Neuroscience
Stato di pubblicazionePubblicato - 1999
Pubblicato esternamente

Keywords

  • Acetylcholine receptor
  • congenital myasthenic syndrome

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