Cardiac Unloading Alters Contractility and Calcium Homeostasis in Ventricular Myocytes

Abstract

M. Ritter, Z. Su, S. Xu, J. Shelby and W. H. Barry. Cardiac Unloading Alters Contractility and Calcium Homeostasis in Ventricular Myocytes. Journal of Molecular and Cellular Cardiology (2000) 32, 577–584. 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 ([Ca2+]itransients, SR Ca2+content); and L-type Ca2+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 [Ca2+]itransient were observed in myocytes from unloaded hearts as compared with controls. Transsarcolemmal ICa,Land INa/Cadensities, and SR Ca2+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 Ca2+buffers, may contribute to the increase in the [Ca2+]itransient in this model.