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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/H169    most recent 00007.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Saini, H. K. Articles by Dhalla, N. S. Search for Related Content PubMed PubMed Citation Articles by Saini, H. K. Articles by Dhalla, N. S.

Sarcolemmal cation channels and exchangers modify the increase in intracellular calcium in cardiomyocytes on inhibiting Na⁺-K⁺-ATPase

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

Submitted 3 January 2007 ; accepted in final form 21 February 2007

Although inhibition of the sarcolemmal (SL) Na⁺-K⁺-ATPase is known to cause an increase in the intracellular concentration of Ca²⁺ ([Ca²⁺]_i) by stimulating the SL Na⁺/Ca²⁺ exchanger (NCX), the involvement of other SL sites in inducing this increase in [Ca²⁺]_i is not fully understood. Isolated rat cardiomyocytes were treated with or without different agents that modify Ca²⁺ movements by affecting various SL sites and were then exposed to ouabain. Ouabain was observed to increase the basal levels of both [Ca²⁺]_i and intracellular Na⁺ concentration ([Na⁺]_i) as well as to augment the KCl-induced increases in both [Ca²⁺]_i and [Na⁺]_i in a concentration-dependent manner. The ouabain-induced changes in [Na⁺]_i and [Ca²⁺]_i were attenuated by treatment with inhibitors of SL Na⁺/H⁺ exchanger and SL Na⁺ channels. Both the ouabain-induced increase in basal [Ca²⁺]_i and augmentation of the KCl response were markedly decreased when cardiomyocytes were exposed to 0–10 mM Na⁺. Inhibitors of SL NCX depressed but decreasing extracellular Na⁺ from 105–35 mM augmented the ouabain-induced increase in basal [Ca²⁺]_i and the KCl response. Not only was the increase in [Ca²⁺]_i by ouabain dependent on the extracellular Ca²⁺ concentration, but it was also attenuated by inhibitors of SL L-type Ca²⁺ channels and store-operated Ca²⁺ channels (SOC). Unlike the SL L-type Ca²⁺-channel blocker, the blockers of SL Na⁺ channel and SL SOC, when used in combination with SL NCX inhibitor, showed additive effects in reducing the ouabain-induced increase in basal [Ca²⁺]_i. These results support the view that in addition to SL NCX, SL L-type Ca²⁺ channels and SL SOC may be involved in raising [Ca²⁺]_i on inhibition of the SL Na⁺-K⁺-ATPase by ouabain. Furthermore, both SL Na⁺/H⁺ exchanger and Na⁺ channels play a critical role in the ouabain-induced Ca²⁺ increase in cardiomyocytes.

sodium-calcium exchanger; sodium-hydrogen exchanger; sarcolemmal Ca²⁺ transport