Contractile activation and the effects of 2,3-butanedione monoxime (BDM) in skinned cardiac preparations from normal and dystrophic mice (129/ReJ).

Abstract

Small cardiac myofibrillar preparations were obtained from the right ventricle of normal (129/ReJ) and dystrophic (129/ReJ dy/dy) mice and were chemically skinned in a relaxing solution by exposure to Triton X-100 (3% v/v). (2) The isometric force produced in these skinned cardiac preparations at different sarcomere lengths was measured in solutions of different [Ca2+] and ionic strength. The effect of the negative inotropic drug 2,3-butanedione monoxime (BDM), which is known to act at the myofibrillar level was also investigated. (3) The murine cardiac preparation from normal animals was found to develop 50% maximal force at a pCa (= -log10[Ca2+]) of 5.59 +/- 0.08 and 5.94 +/- 0.03 (mean +/- SD) under physiological (ionic equivalents concentration, I = 154 mM; pH 7.10; [Mg2+] 1 mM) and low ionic strength (I = 94 mM; pH 7.10; [Mg2+] 1 mM) conditions respectively. The isometric force curves were significantly shallower at low ionic strength (Hill coefficient, 1.8 +/- 0.1) than at physiological ionic strength (Hill coefficient, 2.6 +/- 0.3) and the sarcomere length effect on the force-pCa relation was markedly reduced at lower ionic strength. (4) Increasing BDM concentrations in solutions up to 100 mM reduced the maximum Ca2+-activated force of cardiac preparations from normal mice to less than 6% of the control values in a dose dependent fashion. BDM also rendered the cardiac preparations less sensitive to Ca2+ by a factor of up to 1.5 in a process which showed saturation at BDM concentrations higher than 15 mM.(ABSTRACT TRUNCATED AT 250 WORDS)