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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/H1254    most recent 00964.2006v1 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 (5) Citing Articles via Google Scholar Google Scholar Articles by Yamamoto, T. Articles by Matsubara, H. Search for Related Content PubMed PubMed Citation Articles by Yamamoto, T. Articles by Matsubara, H.

Enhanced activity of ventricular Na⁺-HCO₃^– cotransport in pressure overload hypertrophy

¹Department of Cardiology and Vascular Regenerative Medicine, and ²Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan; and ³Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah

Submitted 6 September 2006 ; accepted in final form 8 March 2007

The Na⁺-HCO₃^– cotransporter (NBC) plays a key role in intracellular pH (pH_i) regulation in normal ventricular muscle. However, the state of NBC in nonischemic hypertrophied hearts is unresolved. In this study, we examined functional and molecular properties of NBC in adult rat ventricular myocytes. The cells were enzymatically isolated from both normal and hypertrophied hearts. Ventricular hypertrophy was induced by pressure overload created by suprarenal abdominal aortic constriction of 50% for 7 wk. pH_i was measured in single cells using the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)5-(6)carboxyfluorescein. Real-time PCR analysis was used to quantitatively assess expression of NBC-encoding mRNA, including SLC4A4 (encoding electrogenic NBC, NBCe1) and SLC4A7 (electroneutral NBC, NBCn1). Our results demonstrate that: 1) mRNA levels of both the electrogenic NBCe1 (SLC4A4) and electroneutral NBCn1 (SLC4A7) forms of NBC were increased by aortic constriction, 2) the onset of NBC upregulation occurred within 3 days after constriction, 3) normal and hypertrophied ventricles displayed regional differences in NBC expression, 4) acid extrusion via NBC (J_NBC) was increased significantly in hypertrophied myocytes, 5) although acid extrusion via Na⁺/H⁺ exchange was also increased in hypertrophied myocytes, the relative enhancement of J_NBC was larger, 6) membrane depolarization markedly increased J_NBC in hypertrophied myocytes, and 7) losartan, an ANG II AT₁ receptor antagonist, significantly attenuated the upregulation of both NBCs induced by 3 wk of aortic constriction. Enhanced NBC activity during hypertrophic development provides a mechanism for intracellular Na⁺ overload, which may render the ventricles more vulnerable to Ca²⁺ overload during ischemia-reperfusion.

cardiac myocytes; intracellular pH regulation; messenger ribonucleic acid; polymerase chain reaction

This article has been cited by other articles:

				E. Boedtkjer, J. Praetorius, E.-M. Fuchtbauer, and C. Aalkjaer Antibody-independent localization of the electroneutral Na+-HCO3- cotransporter NBCn1 (slc4a7) in mice Am J Physiol Cell Physiol, February 1, 2008; 294(2): C591 - C603. [Abstract] [Full Text] [PDF]