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Effect of Na+ reduction and monensin on ion content and contractile response in normoxic and ischaemic reperfused rat hearts
Author(s) -
Ende R.,
Guttmann I.,
Scheufler E.,
Pfaffendorf M.,
Zwieten PA
Publication year - 1995
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1995.tb00276.x
Subject(s) - monensin , medicine , chemistry , cardiology , biochemistry
Summary— The possibility was explored whether the functional properties of Na+/Ca 2+ exchange are altered after ischaemia, thereby contributing to the elevated intracellular (i) Ca 2+ levels in ischaemic reperfused hearts. The intracellular Na+, K+ and Ca 2+ contents in rat Langendorff heart preparations were determined by atomic absorption spectrometry under normoxic conditions, after ischaemia (30 min) and after ischaemia (30 min) plus reperfusion (30 min). In addition, the influence of modulating the Na+ gradient (Na+ o /Na+ i ) across the sarcolemma was studied with respect to cardiac contractility and intracellular ion content. This was done by either decreasing extracellular (o) Na+ or by increasing Na+ i with monensin, both in normoxic and reperfused hearts. Both Na+ o reduction and monensin led to an increase in contractility and coronary flow, an effect which was nearly abolished in reperfused hearts. Under normoxic conditions the intracellular ion contents amounted to Na+ = 12.4 ± 0.4, K+ = 99.0 ± 3.1 and Ca 2+ = 0.64 ± 0.02 mmol/kg cell (means ± SEM, n = 7). In normoxic hearts, lowering Na+ o reduced and monensin increased Na+ i , thereby both leading to a decrease in Na+ gradient; no effect on total Ca 2+ i content was observed. Na+ i increased twofold after ischaemia as compared to the normoxic situation, an effect which was aggravated (4 fold increase) in reperfused hearts. The opposite effects were observed for K+ i with a 25% decrease after ischaemia and a 40% decrease in reperfused hearts. Only after ischaemia plus reperfusion was Ca 2+ i increased (6 fold). In reperfused hearts, lowering Na+ o again reduced and monensin increased Na+ i , whereas a further rise in Ca 2+ i was now observed depending on the Na+ gradient across the sarcolemma: the larger the drop in Na+ gradient, the more pronounced the increase in Ca 2+ i in the reperfused heart. We conclude that the Ca 2+ i increase in reperfused hearts can be modulated by changing the Na+ gradient across the sarcolemma. This suggests that inhibited or reversed Na+/Ca 2+ exchange is predominantly responsible for the rise in Ca 2+ i in ischaemic hearts that are subjected to reperfusion.