title: Intermittent hypoxia protects cardiomyocytes against ischemia-reperfusion injury-induced alterations in Ca2+ homeostasis and contraction via the sarcoplasmic reticulum and Na+/Ca2+ exchange mechanisms.
abstract: We have previously demonstrated that intermittent high-altitude (IHA) hypoxia significantly attenuates ischemia-reperfusion (I/R) injury-induced excessive increase in resting intracellular Ca(2+) concentrations ([Ca(2+)](i)). Because the sarcoplasmic reticulum (SR) and Na(+)/Ca(2+) exchanger (NCX) play crucial roles in regulating [Ca(2+)](i) and both are dysfunctional during I/R, we tested the hypothesis that IHA hypoxia may prevent I/R-induced Ca(2+) overload by maintaining Ca(2+) homeostasis via SR and NCX mechanisms. We thus determined the dynamics of Ca(2+) transients and cell shortening during preischemia and I/R injury in ventricular cardiomyocytes from normoxic and IHA hypoxic rats. IHA hypoxia did not affect the preischemic dynamics of Ca(2+) transients and cell shortening, but it significantly suppressed the I/R-induced increase in resting [Ca(2+)](i) levels and attenuated the depression of the Ca(2+) transients and cell shortening during reperfusion. Moreover, IHA hypoxia significantly attenuated I/R-induced depression of the protein contents of SR Ca(2+) release channels and/or ryanodine receptors (RyRs) and SR Ca(2+) pump ATPase (SERCA2) and SR Ca(2+) release and uptake. In addition, a delayed decay rate time constant of Ca(2+) transients and cell shortening of Ca(2+) transients observed during ischemia was accompanied by markedly inhibited NCX currents, which were prevented by IHA hypoxia. These findings indicate that IHA hypoxia may preserve Ca(2+) homeostasis and contraction by preserving RyRs and SERCA2 proteins as well as NCX activity during I/R.
authors.affiliation: Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, 225 Chong Qing Nan Rd., #1 Bldg., Shanghai 200025, China.
authors.forename: Le
authors.initials: L
authors.lastname: Chen
authors.forename: Xi-Yuan
authors.initials: XY
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ji-Dong
authors.initials: JD
authors.lastname: Fu
authors.forename: Zhao-Nian
authors.initials: ZN
authors.lastname: Zhou
authors.forename: Huang-Tian
authors.initials: HT
authors.lastname: Yang
mesh_terms: D000531:Altitude; D000818:Animals; D002110:Caffeine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006706:Homeostasis; D000860:Hypoxia; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: C506948:Atp2a2 protein, rat; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D012964:Sodium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium