The Qgamma component of intra-membrane charge movement is present in mammalian muscle fibres, but suppressed in the absence of S100A1.

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TitleThe Qgamma component of intra-membrane charge movement is present in mammalian muscle fibres, but suppressed in the absence of S100A1.
Publication TypeJournal Article
Year of Publication2009
AuthorsProsser, BL, Hernández-Ochoa, EO, Zimmer, DB, Schneider, MF
JournalJ Physiol
IssuePt 18
Date Published2009 Sep 15
KeywordsAnimals, Cell Membrane, Cells, Cultured, Ion Channel Gating, Membrane Potentials, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Cells, Ryanodine Receptor Calcium Release Channel, S100 Proteins

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.

Alternate JournalJ. Physiol. (Lond.)
PubMed ID19651767
PubMed Central IDPMC2766655
Grant ListR01 AR055099-26 / AR / NIAMS NIH HHS / United States
R01 QR055099 / / PHS HHS / United States
T32 AR007592 / AR / NIAMS NIH HHS / United States