Enhanced SR function in saponin-treated ventricular trabeculae from rabbits with heart failure

Denvir, M.A., MacFarlane, N., Miller, D.J. and Cobbe, S. (1996) Enhanced SR function in saponin-treated ventricular trabeculae from rabbits with heart failure. American Journal of Physiology, 271(3 Pt 2), H850-H859. (PMID:8853317)

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Cardiac sarcoplasmic reticulum (SR) Ca(2+)-loading ability was assessed in a coronary artery ligation model of heart failure. Heart failure was produced in New Zealand White rabbits by ligation of the left marginal coronary artery. Sham-operated animals were used as controls. After hemodynamic and echocardiographic assessment 8 wk after coronary ligation, a free-running trabecula was isolated from the left or right ventricle, mounted for isometric tension measurement, and permeabilized with the chemical skinning agent saponin, leaving the SR functionally intact. The SR was Ca2+ loaded by exposure of the preparation to a mock intracellular solution with a Ca2+ concentration ([Ca2+]) of 150-300 nM. The amplitude of the caffeine-induced contracture was used as a measure of Ca2+ loaded by the SR. The same preparation was then treated with Triton X-100 to disrupt all cell membranes, and Ca2+ sensitivity {expressed as [Ca2+] required to produce 50% of maximal activation (pCa50)} of isometric tension production and maximum Ca2+ activated force (Cmax) were measured. Ligated animals demonstrated enhanced SR Ca(2+)-loading ability that correlated with the degree of left ventricular dysfunction. Enhanced SR Ca2+ loading was associated with evidence of SR Ca2+ overload revealed as spontaneous tension oscillations. Cmax and pCa50 were not significantly different from controls. Increased SR Ca(2+)-loading ability may predispose the SR to Ca2+ overload and could contribute to both contractile dysfunction and arrhythmogenesis in heart failure.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Miller, Dr David and MacFarlane, Professor Niall and Cobbe, Professor Stuart
Authors: Denvir, M.A., MacFarlane, N., Miller, D.J., and Cobbe, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:American Journal of Physiology

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