Cardiac unloading alters contractility and calcium homeostasis in ventricular myocytes.
Altered cardiac workload has an important effect on myocyte structure and function. Cardiac hypertrophy resulting from an increase in load has been studied extensively in the past. However, the effects of unloading and atrophy have recently become of more interest since devices for mechanical left ventricular unloading have been introduced into clinical practice for the treatment of patients with terminal heart failure, and a resulting improved cardiac and myocyte contractility have been reported. We used the heterotopic abdominal mouse heart transplant model in order to study the effects of 5 days of unloading on cell size (confocal microscopy), contractility (fractional shortening: video motion), calcium homeostasis ([Ca(2+)](i)transients, SR Ca(2+)content); and L-type Ca(2+)and sodium/calcium exchanger currents (whole cell patch clamp technique). We found unloading caused decreased cell volume consistent with atrophy. An increased fractional shortening and [Ca(2+)](i)transient were observed in myocytes from unloaded hearts as compared with controls. Transsarcolemmal I(Ca,L)and I(Na/Ca)densities, and SR Ca(2+)content were unaltered, as was membrane capacitance. A reduction in cell volume with mainteinance of internal and surface membrane areas, and/or a decrease in concentration of cellular protein Ca(2+)buffers, may contribute to the increase in the [Ca(2+)](i)transient in this model.
Ritter
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Division of Cardiology, University of Utah Health Science Center, Salt Lake City, UT 84132, USA.
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles; D006706:Homeostasis; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D018487:Ventricular Dysfunction, Left
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium