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Metabolic regulation of Ca2+ release in permeabilized mammalian skeletal muscle fibres. J Physiol 2003 Mar 01;547(Pt 2):453-62



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Pubmed Central ID




Scopus ID

2-s2.0-0037337898 (requires institutional sign-in at Scopus site)   48 Citations


In the present study, the link between cellular metabolism and Ca2+ signalling was investigated in permeabilized mammalian skeletal muscle. Spontaneous events of Ca2+ release from the sarcoplasmic reticulum were detected with fluo-3 and confocal scanning microscopy. Mitochondrial functions were monitored by measuring local changes in mitochondrial membrane potential (with the potential-sensitive dye tetramethylrhodamine ethyl ester) and in mitochondrial [Ca2+] (with the Ca2+ indicator mag-rhod-2). Digital fluorescence imaging microscopy was used to quantify changes in the mitochondrial autofluorescence of NAD(P)H. When fibres were immersed in a solution without mitochondrial substrates, Ca2+ release events were readily observed. The addition of L-glutamate or pyruvate reversibly decreased the frequency of Ca2+ release events and increased mitochondrial membrane potential and NAD(P)H production. Application of various mitochondrial inhibitors led to the loss of mitochondrial [Ca2+] and promoted spontaneous Ca2+ release from the sarcoplasmic reticulum. In many cases, the increase in the frequency of Ca2+ release events was not accompanied by a rise in global [Ca2+]i. Our results suggest that mitochondria exert a negative control over Ca2+ signalling in skeletal muscle by buffering Ca2+ near Ca2+ release channels.

Author List

Isaeva EV, Shirokova N


Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antimycin A
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Drug Combinations
Mitochondria, Muscle
Muscle Fibers, Skeletal
Muscle, Skeletal
Rats, Sprague-Dawley
Ruthenium Compounds
Signal Transduction