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Schwoerer A.P.,University of Hamburg | Schwoerer A.P.,German Center for Cardiovascular Research Hamburg Kiel Luebeck | Neef S.,University of Gottingen | Broichhausen I.,University of Hamburg | And 25 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2013

Cardiac atrophy as a consequence of mechanical unloading develops following exposure to microgravity or prolonged bed rest. It also plays a central role in the reverse remodelling induced by left ventricular unloading in patients with heart failure. Surprisingly, the intracellular Ca2+ transients which are pivotal to electromechanical coupling and to cardiac plasticity were repeatedly found to remain unaffected in early cardiac atrophy. To elucidate the mechanisms underlying the preservation of the Ca2+ transients, we investigated Ca2+ cycling in cardiomyocytes from mechanically unloaded (heterotopic abdominal heart transplantation) and control (orthotopic) hearts in syngeneic Lewis rats. Following 2 weeks of unloading, sarcoplasmic reticulum (SR) Ca2+ content was reduced by ~55 %. Atrophic cardiac myocytes also showed a much lower frequency of spontaneous diastolic Ca 2+ sparks and a diminished systolic Ca2+ release, even though the expression of ryanodine receptors was increased by ~30 %. In contrast, current clamp recordings revealed prolonged action potentials in endocardial as well as epicardial myocytes which were associated with a two to fourfold higher sarcolemmal Ca2+ influx under action potential clamp. In addition, Cav1.2 subunits which form the pore of L-type Ca2+ channels (LTCC) were upregulated in atrophic myocardium. These data suggest that in early cardiac atrophy induced by mechanical unloading, an augmented sarcolemmal Ca2+ influx through LTCC fully compensates for a reduced systolic SR Ca2+ release to preserve the Ca2+ transient. This interplay involves an electrophysiological remodelling as well as changes in the expression of cardiac ion channels. © 2013 The Author(s).

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