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Am J Physiol Heart Circ Physiol 280: H1376-H1382, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 3, H1376-H1382, March 2001

In vivo regulation of Na/Ca exchanger expression by adrenergic effectors

Kish L. Golden1, Jun Ren2, Jessica O'Connor1, Andrea Dean1, Stephen E. DiCarlo1, and James D. Marsh1

1 Program in Molecular and Cellular Cardiology and Department of Physiology, Wayne State University, Detroit, Michigan 48201; and 2 Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, North Dakota 58202

The Na/Ca exchanger encoded by the NCX1 gene plays an important role in calcium homeostasis in cardiac muscle. We previously identified three in vitro signaling pathways that are of major importance in the regulation of Na/Ca exchanger gene expression in neonatal cardiac myocytes, the protein kinase A (PKA) and protein kinase C (PKC) pathways, and intracellular Ca2+. To determine whether these pathways are important in vivo, we stimulated the PKA and PKC pathways and examined functional expression of the Na/Ca exchanger in adult rat heart. After a 3- and 7-day treatment, norepinephrine (200 µg · kg-1 · h-1), isoproterenol (150 µg · kg-1 · h-1), and phenylephrine (200 µg · kg-1 · h-1) each stimulated a significant increase in NCX1 mRNA levels (35-85%, P < 0.05). Norepinephrine also stimulated a 35% increase in protein abundance (P < 0.05), a 20% decrease in relaxation duration (P < 0.05), and a 25% reduction in the fluorescence decay constant (P < 0.05) after a 7-day treatment. We conclude that a 7-day treatment of alpha - and beta -adrenergic agonists increases the expression of functional Na/Ca exchangers in adult rat heart.

calcium; cardiac myocyte


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