6-Hydroxydopamine-induced developmental cardiac alterations in morphology, calmodulin content, and K(2+)-mediated [Ca(2+)](i)Transient of chicken cardiomyocytes.
Calcium and the calcium-calmodulin-mediated processes have been implicated in cardiac hypertrophy. The purpose of this study was to investigate whether there is a potential role played by the calcium-calmodulin processes in cardiac morphogenesis and malformations, especially in the development of cardiac hypertrophy. Recently, the authors reported that 6-hydroxydopamine, an adrenergic neurotoxin can produce malformations in various organs including ventricular septal lesions and cardiac hypertrophy in the developing chicken embryo. Morphological studies revealed areas of coagulative necrosis, with broken nuclear membranes, swollen mitochondria and dilations of the ventricles, as well as thickening of ventricular walls reminiscent of cardiac hypertrophy. The observation that 6-hydroxydopamine treatment on day 3 of incubation produced a dose-dependent increase in both heart and brain calmodulin levels on day 11 of incubation and an increase in the sensitivity to external potassium induction of intracellular free calcium transient in incubation day 14 chicken cardiomyocytes in culture, leading to an increase in intracellular free calcium is reported here. However, sodium/potassium adenosinetriphosphatase activity showed no significant change on days 12 and 16 of incubation. The effect appears to be relatively specific since 5-hydroxydopamine, a chemical isomer of 6-hydroxydopamine, failed to produce a similar sensitivity change of potassium-induced intracellular calcium transient.
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Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA.
Duffield
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D000014:Abnormalities, Drug-Induced / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000196:embryology; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D006332:Cardiomegaly / Q000139:chemically induced*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000378:metabolism; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013565:Sympatholytics / Q000494:pharmacology*; D013997:Time Factors
D002147:Calmodulin; D013565:Sympatholytics; D016627:Oxidopamine; D000251:Adenosine Triphosphatases; D011188:Potassium; D002118:Calcium