Genetic manipulation of calcium-handling proteins in cardiac myocytes. I. Experimental studies

American Journal of Physiology. Heart and Circulatory Physiology
Pierre Coutu, Joseph M Metzger

Abstract

Two genetic experimental approaches, de novo expression of parvalbumin (Parv) and overexpression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), have been shown to increase relaxation rates in myocardial tissue. However, the relative effect of Parv and SERCA2a on systolic function and on beta-adrenergic responsiveness at varied pacing rates is unknown. We used gene transfer in isolated rat adult cardiac myocytes to gain a fuller understanding of Parv/SERCA2a function. As demonstrated previously, when Parv is expressed in elevated concentration (>0.1 mM), the transduced myocytes showed a reduction in sarcomere-shortening amplitude: 129 +/- 17, 81 +/- 8, and 149 +/- 14 nm for control, Parv, and SERCA2a, respectively. At physiological temperature, shortening amplitude responses of Parv and SERCA2a myocytes to the beta-adrenergic agonist isoproterenol (Iso) were not statistically different from that of control myocytes. However, in SERCA2a myocytes, in which baseline was slightly elevated and the Iso-stimulated value was slightly lower, the increase in shortening was slightly less than in Parv or control myocytes: 108 +/- 14, 169 +/- 39, and 34 +/- 12% for control, Parv, and SERCA2a, respectively. In another test set, Parv...Continue Reading

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Citations

Dec 29, 2009·The Journal of Biological Chemistry·Marjorie MailletJeffery D Molkentin
Nov 30, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Rene VandenboomJoseph M Metzger
Jun 3, 2014·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kohga HiranoKohji Fukunaga
Jul 4, 2006·Journal of Molecular and Cellular Cardiology·John J GreenMargaret V Westfall
Mar 19, 2014·Journal of Molecular and Cellular Cardiology·Wang WangJoseph M Metzger
May 12, 2016·Biophysical Journal·Michelle L AspJoseph M Metzger
Aug 31, 2013·Circulation Research·Min Luo, Mark E Anderson
Jun 5, 2007·American Journal of Physiology. Heart and Circulatory Physiology·David W RodenbaughJoseph M Metzger
Aug 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Pierre Coutu, Joseph M Metzger

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