HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/H2790    most recent 00535.2006v2 00535.2006v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) 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.

Modification of intracellular calcium concentration in cardiomyocytes by inhibition of sarcolemmal Na⁺/H⁺ exchanger

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

Submitted 24 May 2006 ; accepted in final form 14 July 2006

Although the Na⁺/H⁺ exchanger (NHE) is considered to be involved in regulation of intracellular Ca²⁺ concentration ([Ca²⁺]_i) through the Na⁺/Ca²⁺ exchanger, the exact mechanisms of its participation in Ca²⁺ handling by cardiomyocytes are not fully understood. Isolated rat cardiomyocytes were treated with or without agents that are known to modify Ca²⁺ movements in cardiomyocytes and exposed to an NHE inhibitor, 5-(N-methyl-N-isobutyl)amiloride (MIA). [Ca²⁺]_i in cardiomyocytes was measured spectrofluorometrically with fura 2-AM in the absence or presence of KCl, a depolarizing agent. MIA increased basal [Ca²⁺]_i and augmented the KCl-induced increase in [Ca²⁺]_i in a concentration-dependent manner. The MIA-induced increase in basal [Ca²⁺]_i was unaffected by extracellular Ca²⁺, antagonists of the sarcolemmal (SL) L-type Ca²⁺ channel, and inhibitors of the SL Na⁺/Ca²⁺ exchanger, SL Ca²⁺ pump ATPase and mitochondrial Ca²⁺ uptake. However, the MIA-induced increase in basal [Ca²⁺]_i was attenuated by inhibitors of SL Na⁺-K⁺-ATPase and sarcoplasmic reticulum (SR) Ca²⁺ transport. On the other hand, the MIA-mediated augmentation of the KCl response was dependent on extracellular Ca²⁺ concentration and attenuated by agents that inhibit SL L-type Ca²⁺ channels, the SL Na⁺/Ca²⁺ exchanger, SL Na⁺-K⁺-ATPase, and SR Ca²⁺ release channels and the SR Ca²⁺ pump. However, the effect of MIA on the KCl-induced increase in [Ca²⁺]_i remained unaffected by treatment with inhibitors of SL Ca²⁺ pump ATPase and mitochondrial Ca²⁺ uptake. MIA and a decrease in extracellular pH lowered intracellular pH and increased basal [Ca²⁺]_i, whereas a decrease in extracellular pH, in contrast to MIA, depressed the KCl-induced increase in [Ca²⁺]_i in cardiomyocytes. These results suggest that NHE may be involved in regulation of [Ca²⁺]_i and that MIA-induced increases in basal [Ca²⁺]_i, as well as augmentation of the KCl-induced increase in [Ca²⁺]_i, in cardiomyocytes are regulated differentially.

sodium-potassium adenosinetriphosphatase; calcium-handling proteins; sarcolemmal calcium transport; sarcoplasmic reticulum calcium transport; 5-(N-methyl-N-isobutyl) amiloride

This article has been cited by other articles:

				H. K. Saini and N. S. Dhalla Sarcolemmal cation channels and exchangers modify the increase in intracellular calcium in cardiomyocytes on inhibiting Na+-K+-ATPase Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H169 - H181. [Abstract] [Full Text] [PDF]