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Involvement of Na⁺/Ca²⁺ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

Submitted 8 June 2005 ; accepted in final form 5 September 2005

Although sarcolemmal (SL) Na⁺/Ca²⁺ exchanger is known to regulate the intracellular Ca²⁺ concentration ([Ca²⁺]_i), its involvement in catecholamine-induced increase in [Ca²⁺]_i is not fully understood. To gain some information in this regard, isolated rat cardiomyocytes were treated with different agents, which are known to modify Ca²⁺ movements, in the absence or presence of a -adrenoceptor agonist, isoproterenol, and [Ca²⁺]_i in cardiomyocytes was determined spectrofluorometrically with fura-2 AM. Treatment with isoproterenol did not alter [Ca²⁺]_i in quiescent cardiomyocytes, whereas the ATP (purinergic receptor agonist)-induced increase in [Ca²⁺]_i was significantly potentiated by isoproterenol. Unlike ryanodine and cyclopiazonic acid, which affect the sarcoplasmic reticulum function, SL L-type Ca²⁺ channel blockers verapamil and diltiazem, as well as a SL Ca²⁺-pump inhibitor, vanadate, caused a significant depression in the isoproterenol-induced increase in [Ca²⁺]_i. The SL Na⁺/Ca²⁺ exchange blockers amiloride, Ni²⁺, and KB-R7943 also attenuated the isoproterenol-mediated increase in [Ca²⁺]_i. Combination of KB-R7943 and verapamil showed additive inhibitory effects on the isoproterenol-induced increase in [Ca²⁺]_i. The isoproterenol-induced increase in [Ca²⁺]_i in KCl-depolarized cardiomyocytes was augmented by low Na⁺; this augmentation was significantly depressed by treatment with KB-R7943. The positive inotropic action of isoproterenol in isolated hearts was also reduced by KB-R7943. These data suggest that in addition to SL L-type Ca²⁺ channels, SL Na⁺/Ca²⁺ exchanger seems to play an important role in catecholamine-induced increase in [Ca²⁺]_i in cardiomyocytes.

sodium/calcium exchanger; L-type calcium channels; calcium-pump adenosine triphosphatase; calcium-release channels; cardiomyocyte calcium handling

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