Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat heart

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 2; pp. H497 - H503
• Main Authors: Huang, M.-H, Bahl, J. J, Wu, Y, Hu, F, Larson, D. F, Roeske, W. R, Ewy, G. A
• Format: Journal Article
• Language: English
• Published: United States 01.02.2005
• Subjects: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists - pharmacology; Animals; Calcium - metabolism; Calcium Channels - metabolism; Cells, Cultured; Membrane Potentials - physiology; Myocardial Contraction - physiology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - physiology; Norepinephrine - pharmacokinetics; Norepinephrine Plasma Membrane Transport Proteins; Phenylethanolamine N-Methyltransferase - genetics; Phenylethanolamine N-Methyltransferase - metabolism; Rats; Receptors, Adrenergic, beta-1 - metabolism; RNA, Messenger - metabolism; Symporters - metabolism; Tritium; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00591.2004

1 Department of Internal Medicine, Cardiology Division, University of Texas Medical Branch, Galveston, Texas; 2 Department of Medicine, Cardiology Division and Sarver Heart Center, and Departments of 3 Pharmacology and Toxicology and 4 Surgery, University of Arizona College of Medicine, Tucson, Arizona Submitted 15 June 2004 ; accepted in final form 22 September 2004 Intrinsic cardiac adrenergic (ICA) cells in developing rat heart constitute a novel adrenergic signaling system involved in cardiac regulation. Regulatory mechanisms of ICA cells remain to be defined. Immunohistochemical study of fetal rat hearts demonstrated ICA cells with catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) and phenylethanolamine N -methyltransferase (PNMT). The mRNA of TH and PNMP was also detected in fetal rat hearts before sympathetic innervation. Immunoreactivity of norepinephrine transporter (NET) was localized to ICA cells in rat heart tissue and primary cell culture. For the functional study, the activity of intracellular Ca 2+ concentration ([Ca 2+ ] i ) transients was quantified by a ratio fluorescent spectrometer in cultured ICA cells and myocytes. ICA cells generated spontaneous [Ca 2+ ] i transients that were eliminated by tetrodotoxin or Ca 2+ -free solutions and showed greatly reduced amplitude with the addition of L-type Ca 2+ channel blocker nifedipine. [ 3 H]norepinephrine studies demonstrate release and uptake of norepinephrine. Functional interaction between catecholamines produced by the ICA cells and cocultured myocytes was evident by the effect of the -adrenergic blocker atenolol eliciting a dose-dependent reduction in the amplitude and frequency of [Ca 2+ ] i transients of beating myocytes. Hypoxia inhibited [Ca 2+ ] i transient activity of ICA cells, which subsequently produced a reoxygenation-mediated rebound augmentation of [Ca 2+ ] i transients. We conclude that ICA cells are capable of catecholamine synthesis, release, and uptake. They generate spontaneous [Ca 2+ ] i transient activity that can be regulated by oxygen tension. ICA cells may provide an alternative adrenergic supply to maintain cardiac contractile and pacemaker function at rest and during stress in the absence of sympathetic innervation. calcium; hypoxia/reoxygenation; intrinsic cardiac adrenergic cells; myocytes; norepinephrine Address for reprint requests and other correspondence: M.-H. Huang, Univ. of Texas Medical Branch, Dept. of Internal Medicine/Cardiology Division, 5.106 John Sealy Annex, 301 University Blvd., Galveston, TX 77555-0553 (E-mail: mihuang{at}utmb.edu )