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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 · h1),
isoproterenol (150 µg · kg1 · h1), and
phenylephrine (200 µg · kg1 · h1) 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 
- and 
-adrenergic agonists increases the
expression of functional Na/Ca exchangers in adult rat heart.
calcium; cardiac myocyte
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