AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol (February 12, 2004). doi:10.1152/ajpheart.01096.2003
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Submitted on November 24, 2003
Accepted on February 6, 2004

Insights into cardioprotection obtained from study of cellular Ca2+ handling in true hibernating myocardium

Atsuko Yatani1*, Song-Jung Kim1, Raymond K. Kudej1, Qian Wang1, Christophe Depre1, Keiichi Irie1, Evangelia G. Kranias2, Stephen F. Vatner1, and Dorothy E. Vatner1

1 Cardiovascular Research Institute and Department of Cell Biology & Molecular Medicine, University of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark, NJ, USA
2 Department of Pharmacology & Cell Biophysiology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA

* To whom correspondence should be addressed. E-mail: yataniat{at}umdnj.edu.

Mammalian hibernators exhibit remarkable resistance to low body temperature, whereas non-hibernating (NHB) mammals develop ventricular dysfunction and arrhythmias. To investigate this adaptive change, we compared contractile and electrophysiological properties of left ventricular (LV) myocytes isolated from hibernating (HB) woodchucks (M. Monax) and from control NHB woodchucks. The major findings of this study were: (1) the action potential duration (APD) in HB myocytes were significantly shorter than in NHB myocytes, but the amplitude of peak contraction was unchanged. (2) HB myocytes had a decreased (33%) L-type Ca2+ current (ICa) density and twofold faster ICa inactivation but no change in the current-voltage relationship. (3) There was no change in the density of inward rectifier K+ current, the transient outward K+ current or Na+/Ca2+ exchange current (INa/Ca), but HB myocyte had increased sarcoplasmic reticulum (SR) Ca2+ content, as estimated from caffeine-induced INa/Ca. (4) The expression of the L-type Ca2+ channe {alpha}1C subunit was decreased by 30% in HB hearts. (5) mRNA and protein levels of SERCA2a, phospholamban (PLB) and Na+/Ca2+ exchanger (NCX) showed a pattern consistent with functional measurements: SERCA2a was increased and PLB was decreased in HB relative to NHB hearts, with no change in NCX. Thus, a reduction of Ca2+ channel density and faster ICa inactivation coupled to enhanced SR Ca2+ release may underlie shorter action potential but maintain contractility in HB hearts. These changes may account for natural resistance to Ca2+ overload-related ventricular dysfunction and point to an important cardioprotective mechanism during true hibernation.




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