Linked Life Data

19651767

Source:http://linkedlifedata.com/resource/pubmed/id/19651767

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 18
pubmed:dateCreated
2009-9-15
pubmed:abstractText
S100A1 is a Ca(2+) binding protein that modulates excitation-contraction (EC) coupling in skeletal and cardiac muscle. S100A1 competes with calmodulin for binding to the skeletal muscle SR Ca(2+) release channel (the ryanodine receptor type 1, RyR1) at a site that also interacts with the C-terminal tail of the voltage sensor of EC coupling, the dihydropyridine receptor. Ablation of S100A1 leads to delayed and decreased action potential evoked Ca(2+) transients, possibly linked to altered voltage sensor activation. Here we investigate the effects of S100A1 on voltage sensor activation in skeletal muscle utilizing whole-cell patch clamp electrophysiology to record intra-membrane charge movement currents in isolated flexor digitorum brevis (FDB) muscle fibres from wild-type and S100A1 knock-out (KO) mice. In contrast to recent reports, we found that FDB fibres exhibit two distinct components of intra-membrane charge movement, an initial rapid component (Q(beta)), and a delayed, steeply voltage dependent 'hump' component (Q(gamma)) previously recorded primarily in amphibian but not mammalian fibres. Surprisingly, we found that Q(gamma) was selectively suppressed in S100A1 KO fibres, while the Q(beta) component of charge movement was unaffected. This result was specific to S100A1 and not a compensatory result of genetic manipulation, as transient intracellular application of S100A1 restored Q(gamma). Furthermore, we found that exposure to the RyR1 inhibitor dantrolene suppressed a similar component of charge movement in FDB fibres. These results shed light on voltage sensor activation in mammalian muscle, and support S100A1 as a positive regulator of the voltage sensor and Ca(2+) release channel in skeletal muscle EC coupling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1469-7793
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
587
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4523-41
pubmed:dateRevised
2011-2-24
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The Qgamma component of intra-membrane charge movement is present in mammalian muscle fibres, but suppressed in the absence of S100A1.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural