Why the study?
Does increased Na,Ca-exchanger protein expression in rat cardiomyocytes with CHF reduce tolerance to extracellular Ca2+?
Does increased Na,Ca-exchanger protein expression in rat cardiomyocytes with CHF reduce tolerance to extracellular Ca2+?
Cardiomyocytes from rats with CHF are more susceptible to calcium overload due to increased capacity for Na,Ca-exchange.
CHF rat cardiomyocytes show reduced Ca2+ tolerance with higher NCX; hypothesis-generating and should not yet change practice.
During ischaemia and reperfusion the intracellular Na+ concentration is elevated in the cardiomyocytes and the cells are depolarized, both favouring reverse mode Na,Ca-exchange loading of the cell with Ca2+. We examined whether cardiomyocytes from rats with congestive heart failure (CHF) and younger rats (HINCX) which both have a high expression of the Na,Ca-exchanger protein (NCX) showed reduced tolerance to extracellular Ca2+. The CHF was induced in Isofluran anaesthetized rats by left coronary artery ligation. Isolated cardiomyocytes were loaded with Fura-2AM and 140 mm Na+ and exposed to 0.05 mm Ca2+. Expression of the Na,Ca-exchanger protein was analysed. Fura-2 340/380 ratio rose more rapidly in HINCX and CHF than in SHAM, and the rise was abolished by Ni2+. Hypercontracture developed more frequently in HINCX and CHF than in SHAM cells. The amount of NCX was 54% higher in HINCX and 76% higher in CHF compared with SHAM. Na+-loaded cardiomyocytes from CHF and HINCX rats are more susceptible to Ca2+ overload than SHAM cells because of the increased capacity for Na,Ca-exchange.
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Sjaastad et al. (2002) studied this question.
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