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This Article Full Text Full Text (PDF) All Versions of this Article: 586/1/197    most recent jphysiol.2007.146571v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martins, A. S. Articles by Shirokova, N. Search for Related Content PubMed PubMed Citation Articles by Martins, A. S. Articles by Shirokova, N. Related Collections Cellular

¹ Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA

Ca²⁺ sparks, localized elevations in cytosolic [Ca²⁺], are rarely detected in intact adult mammalian skeletal muscle under physiological conditions. However, they have been observed in permeabilized cells and in intact fibres subjected to stresses, such as osmotic shock and strenuous exercise. Our previous studies indicated that an excess in cellular reactive oxygen species (ROS) generation over the ROS scavenging capabilities could be one of the up-stream causes of Ca²⁺ spark appearance in permeabilized muscle fibres. Here we tested whether the cytosolic ROS balance is compromised in intact skeletal muscle fibres that underwent osmotic shock and whether this misbalance contributes to unmasking Ca²⁺ sparks. Spontaneous Ca²⁺ sparks and the rate of ROS generation were assessed with single photon confocal microscopy and fluorescent indicators fluo-4, CM-H₂DCFDA and MitoSOX Red. Osmotic shock produced spontaneous Ca²⁺ sparks and a concomitant significant increase in ROS production. Preincubation of muscle cells with ROS scavengers (e.g. MnTBAP, Mn-cpx 3, TIRON) nearly eliminated Ca²⁺ sparks. In addition, inhibitors of NAD(P)H oxidase (DPI and apocynin) significantly reduced ROS production and suppressed the appearance of Ca²⁺ sparks. Taken together, the data suggest that ROS contribute to the abnormal Ca²⁺ spark activity in mammalian skeletal muscle subjected to osmotic stress and also indicate that NAD(P)H oxidase is a possible source of ROS. We propose that ROS-dependent Ca²⁺ sparks are an important component of adaptive/maladaptive muscle responses under various pathological conditions such as eccentric stretch, osmotic changes during ischaemia and reperfusion, and some muscle diseases.

(Received 12 October 2007; accepted after revision 25 October 2007; first published online 1 November 2007)
Corresponding author N. Shirokova: Department of Pharmacology and Physiology, UMDNJ, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. Email: nshiroko{at}umdnj.edu

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