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Antioxid Redox Signal. 2000 Spring;2(1):55-64.

Oxygen free radicals and excitation-contraction coupling.

Author information

1
UCLA School of Medicine, Department of Medicine (Cardiology), Los Angeles, CA 90095-1679, USA. jgoldhaber@mednet.ucla.edu

Abstract

Oxygen free radicals (OFR) contribute to contractile failure, rigor, and calcium (Ca2+) overload in ischemic/reperfused myocardium. Using both multicellular and isolated single-cell preparations, our laboratory has identified two fundamental mechanisms contributing to the deleterious effects of OFR: (i) impaired myocardial metabolism, and (ii) altered myocardial calcium handling. Impaired metabolism leads to activation of metabolically sensitive K+ currents, which shorten the action potential, thereby decreasing the duration of systole. Ultimately, high-energy phosphate depletion secondary to metabolic failure results in rigor. Altered myocardial Ca2+ handling is evidenced by a decrease in Ca2+ entry via L-type Ca2+ channels [another cause of decreased action potential duration (APD)], a reduction in sarcoplasmic reticulum (SR) Ca2+ content, slowed Ca2+ uptake in diastole, and increased sodium-calcium exchange (NaCaX) activity. The increase in NaCaX activity may contribute to the early increase in developed tension frequently observed in multicellular preparations exposed to free radicals, as well as the SR depletion occurring early on in voltage-clamped isolated cell preparations. Increased NaCaX activity is likely to be a critical factor underlying the late Ca2+ overload that occurs in the setting of increased intracellular Na+, and which leads to irreversible injury. The extent to which free radical-mediated metabolic inhibition participates in the dysfunction of the L-type Ca2+ channel is uncertain. The altered activity of the SR Ca2+ pump and NaCaX are more likely caused by direct actions of OFR on these proteins.

PMID:
11232601
DOI:
10.1089/ars.2000.2.1-55
[Indexed for MEDLINE]

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