Progressive loss of creatine maintains a near normal DeltaG approximately (ATP) in transgenic mouse hearts with cardiomyopathy caused by overexpressing Gsalpha.

Journal of Molecular and Cellular Cardiology
Weiqun ShenJ S Ingwall

Abstract

Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (DeltaG approximately (ATP)), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice overexpressing cardiac Gsalpha, which slowly developed cardiomyopathy. Myocardial energetics measured using (31)P NMR spectroscopy and isovolumic contractile performance were determined in perfused hearts isolated from 5-, 10-, 17-month-old Gsalpha and age-matched littermate wild type (WT) mice. In young Gsalpha hearts, contractile performance was enhanced with near normal cardiac energetics. With age, as contractile performance progressively decreased in Gsalpha hearts, [ATP] and [PCr] progressively decreased while [Pi] increased only modestly; no changes were observed in WT hearts. Myocardial (but not skeletal) [Cr] in Gsalpha mice decreased, beginning at an early age (1.5 months). Consequently, cytosolic [ADP] and the free energy available from ATP hydrolysis were maintained at normal levels in Gsalpha hearts, despite decreased [ATP]. During increased cardiac work caused by supplying isoproterenol, the relationshi...Continue Reading

References

Oct 1, 1986·Journal of the American College of Cardiology·W A Neill, J S Ingwall
Mar 1, 1985·The American Journal of Physiology·R A MeyerM J Kushmerick
Apr 1, 1995·The Journal of Clinical Investigation·C GaudinC J Homcy
May 12, 1998·The American Journal of Physiology·M I Bak, J S Ingwall
Jan 23, 1999·Circulation Research·Y J GengC J Homcy
Jul 14, 2000·Physiological Reviews·M Wyss, R Kaddurah-Daouk
Oct 24, 2006·Journal of Molecular and Cellular Cardiology·Kirsten HoyerJoanne S Ingwall
Mar 16, 2007·The New England Journal of Medicine·Stefan Neubauer
Jul 8, 2008·Journal of Molecular and Cellular Cardiology·Michiel ten HoveStefan Neubauer
Nov 7, 2008·Cardiovascular Research·Joanne S Ingwall

❮ Previous
Next ❯

Citations

Sep 5, 2012·Heart Failure Reviews·Kiterie M E FallerJürgen E Schneider
Dec 17, 2009·Journal of Molecular and Cellular Cardiology·Julian D Widder, Georg Ertl
Aug 31, 2013·Circulation Research·Min Luo, Mark E Anderson
Jan 19, 2012·European Journal of Heart Failure·Hossein ArdehaliMihai Gheorghiade
Oct 8, 2021·Heart Failure Reviews·Annamaria Del FrancoGiuseppe Vergaro
Sep 28, 2010·Biochimica Et Biophysica Acta·Renée Ventura-ClapierFrédéric Joubert

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.