Article

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

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA.
The Journal of Physiology (Impact Factor: 5.04). 09/2009; 587(Pt 18):4523-41. DOI: 10.1113/jphysiol.2009.177238
Source: PubMed

ABSTRACT

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.

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Available from: Erick O Hernández-Ochoa
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    • "Both, skeletal and cardiac ryanodine receptors are regulated this way by S100A1. The Q gamma component activated by S100A1, however , appears not to be linked to gating of dihydropyridine Ca 2+ channels, but is more likely involved in the excitation–contraction coupling machinery (Prosser et al., 2009a). S100A1 also improves Ca 2+ cycling and contractility in cardiac muscle (Most et al., 2007) and increased Ca 2+ release and force of contraction in skinned muscle fibers (Most et al., 2003). "

    Full-text · Dataset · Nov 2013
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    • "Thus, exposure to Dantrolene produced no significant effect on the average peak current density, voltage dependence of activation, voltage dependence of inactivation, or recovery from inactivation of the Na+ current in developing myotubes (Figures 1–3). The inability of Dantrolene to modulate these parameters of the Na+ current in this preparation is consistent with the idea that the Dantrolene-induced inhibition of CaV1.1 observed in previous studies [19, 25, 27] most likely was a consequence of Dantrolene interacting with the EC coupling apparatus at plasma membrane-SR junctions, rather than a general nonspecific depression of plasma membrane excitability. "
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    • "Both, skeletal and cardiac ryanodine receptors are regulated this way by S100A1. The Q gamma component activated by S100A1, however , appears not to be linked to gating of dihydropyridine Ca 2+ channels, but is more likely involved in the excitation–contraction coupling machinery (Prosser et al., 2009a). S100A1 also improves Ca 2+ cycling and contractility in cardiac muscle (Most et al., 2007) and increased Ca 2+ release and force of contraction in skinned muscle fibers (Most et al., 2003). "
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