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Norepinephrine regulates the in vivo expression of the L-type calcium channel

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Abstract

The α1c subunit (DHP receptor) of the L-type Ca2+ channel is important for calcium homeostasis in cardiac muscle. The DHPr provides the primary mechanism for calcium influx during contraction. Published results demonstrate three in vitro signaling pathways that are important in the regulation of DHPr gene expression in neonatal cardiac myocytes, the protein kinase A (PKA), protein kinase C (PKC) pathways, and intracellular calcium. To determine whether these pathways are important in vivo, we treated adult rats with infusions of isoproterenol, or norepinephrine at 200 μg/kg/h and assessed DHPr mRNA and protein levels. Following a 3-day infusion isoproterenol (ISO) and norepinephrine (NE) produced a small but insignificant reduction in DHPr mRNA levels. When the infusions were continued for 7 days isoproterenol increased DHPr mRNA accumulation to control levels while NE stimulated a 35% increase in DHPr mRNA levels and a 35% increase in protein abundance when compared to controls (p < 0.05). Furthermore, contractility and Ca2+ transient measurements of isolated cardiac myocytes from NE infused animals also display shortened duration of contraction/relaxation and increased intracellular free Ca2+ (DFFI) in response to electrical stimulation (p < 0.01). We conclude norepinephrine treatment alters DHPr mRNA and protein levels, and augments excitation-contraction coupling, and thus may be important for modulating cardiac calcium homeostasis in vivo.

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Authors and Affiliations

  1. Program in Molecular and Cellular Cardiology and Department of Physiology and Internal Medicine, Wayne State University, Detroit, MI, USA

    Kish L. Golden, Andrea Dean & James D. Marsh

  2. Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND, USA

    Jun Ren

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  1. Kish L. Golden
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  2. Jun Ren
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  3. Andrea Dean
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  4. James D. Marsh
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Golden, K.L., Ren, J., Dean, A. et al. Norepinephrine regulates the in vivo expression of the L-type calcium channel. Mol Cell Biochem 236, 107–114 (2002). https://doi.org/10.1023/A:1016112617817

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