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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 1
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pubmed:dateCreated |
2006-5-16
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pubmed:abstractText |
Slow-channel congenital myasthenic syndrome, caused by mutations in subunits of the endplate ACh receptor (AChR), results in prolonged synaptic currents and excitotoxic injury of the postsynaptic region by Ca2+ overloading. The Ca2+ overloading could be due entirely to the prolonged openings of the AChR channel or could be abetted by enhanced Ca2+ permeability of the mutant channels. We therefore measured the fractional Ca2+ current, defined as the percentage of the total ACh-evoked current carried by Ca2+ ions (Pf), for AChRs harbouring the alphaG153S or the alphaV249F slow-channel mutation, and for wild-type human AChRs in which Pf has not yet been determined. Experiments were performed in transiently transfected GH4C1 cells and human myotubes with simultaneous recording of ACh-evoked whole-cell currents and fura-2 fluorescence signals. We found that the Pf of the wild-type human endplate AChR was unexpectedly high (Pf approximately 7%), but neither the alphaV249F nor the alphaG153S mutation altered Pf. Fetal human AChRs containing either the wild-type or the mutated alpha subunit had a much lower Pf (2-3%). We conclude that the Ca2+ permeability of human endplate AChRs is higher than that reported for any other human nicotinic AChR, with the exception of alpha7-containing AChRs (Pf > 10%); and that neither the alphaG153S nor the alphaV249F mutations affect the Pf of fetal or adult endplate AChRs. However, the intrinsically high Ca2+ permeability of human AChRs probably predisposes to development of the endplate myopathy when opening events of the AChR channel are prolonged by altered AChR-channel kinetics.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-10716716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-11007310,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-11891309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-12151524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-12508290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-12728262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-12810063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-12909079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-1370370,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-14670366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-14991812,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-15217093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-15746172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-15760934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-15905852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-15907919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-16037088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-16451809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-313017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-438872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-511934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-6287911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-7510879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-7537407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-7619526,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-8841995,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-9221765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-9508804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16527851-9508836
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3751
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
573
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35-43
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16527851-Adult,
pubmed-meshheading:16527851-Animals,
pubmed-meshheading:16527851-Calcium,
pubmed-meshheading:16527851-Cell Line,
pubmed-meshheading:16527851-Humans,
pubmed-meshheading:16527851-Mice,
pubmed-meshheading:16527851-Motor Endplate,
pubmed-meshheading:16527851-Muscle Fibers, Skeletal,
pubmed-meshheading:16527851-Mutagenesis,
pubmed-meshheading:16527851-Neurotoxins,
pubmed-meshheading:16527851-Patch-Clamp Techniques,
pubmed-meshheading:16527851-Pituitary Gland,
pubmed-meshheading:16527851-Protein Subunits,
pubmed-meshheading:16527851-Rats,
pubmed-meshheading:16527851-Receptors, Nicotinic,
pubmed-meshheading:16527851-Synaptic Transmission,
pubmed-meshheading:16527851-Transfection
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pubmed:year |
2006
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pubmed:articleTitle |
The human adult subtype ACh receptor channel has high Ca2+ permeability and predisposes to endplate Ca2+ overloading.
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pubmed:affiliation |
Pasteur Institute -Cenci Bolognetti Foundation & Department of Human Physiology and Pharmacology & Centre of Excellence for Biology and Molecular Medicine, University of Rome La Sapienza, Piazzale Aldo Moro 5; I-00185 Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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