PMID- 10195214
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20071114
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 2
IP  - 3
DP  - 1999 Mar
TI  - Acetylcholine receptor M3 domain: stereochemical and volume contributions to
      channel gating.
PG  - 226-33
AB  - 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.
FAU - Wang, H L
AU  - Wang HL
AD  - Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota
      55905, USA.
FAU - Milone, M
AU  - Milone M
FAU - Ohno, K
AU  - Ohno K
FAU - Shen, X M
AU  - Shen XM
FAU - Tsujino, A
AU  - Tsujino A
FAU - Batocchi, A P
AU  - Batocchi AP
FAU - Tonali, P
AU  - Tonali P
FAU - Brengman, J
AU  - Brengman J
FAU - Engel, A G
AU  - Engel AG
FAU - Sine, S M
AU  - Sine SM
LA  - eng
GR  - NS 31744/NS/NINDS NIH HHS/United States
GR  - NS6277/NS/NINDS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Ion Channels)
RN  - 0 (Receptors, Cholinergic)
SB  - IM
EIN - Nat Neurosci 1999 May;2(5):485
MH  - Amino Acid Sequence/genetics
MH  - Child
MH  - DNA Mutational Analysis
MH  - Humans
MH  - Ion Channel Gating/*physiology
MH  - Ion Channels/*metabolism
MH  - Kinetics
MH  - Male
MH  - Molecular Sequence Data
MH  - Neuromuscular Diseases/genetics/metabolism
MH  - Receptors, Cholinergic/*genetics
MH  - Stereoisomerism
MH  - Syndrome
EDAT- 1999/04/09 02:02
MHDA- 2001/03/23 10:01
CRDT- 1999/04/09 02:02
PHST- 1999/04/09 02:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/09 02:02 [entrez]
AID - 10.1038/6326 [doi]
PST - ppublish
SO  - Nat Neurosci. 1999 Mar;2(3):226-33. doi: 10.1038/6326.