Abstract
The effects of four Ca 2+ binding protein modulators (bepridil, perhexiline, calmidazolium and trifluoperazine) on cardiac myofibrillar ATPase activity in Triton-purified myofibrils prepared from normal dogs, normal hamsters and age/sex (male, 16–20 weeks)-matched myopathic hamsters (BIO 14.6) have been quantitated. When compared with normal hamsters, myopathic hamster myofibrils have a markedly depressed maximum MgATPase activity (178±2 vs. 119±3 nnmol/mg per min, respectively) and a slightly increased requirement of Ca 2+ for half-maximal activation (ED 50;0.66 vs. 0.75 μM free Ca 2+, respectively). Calmidazolium, trifluoperazine and bepridil lower the ED 50 for Ca 2+ in myopathic myofibrils. Moreover, bepridil and trifluoperazine increase maximum myofibrillar MgATPase activity in myopathic hamster myofibrils. In contrast, calmidazolium depresses maximum and stimulates basal MgATPase activities in myopathic and normal hamster myofibrils. Qualitatively, different effects are apparent when these agents are examined in canine myofibrils. Thus, the pharmacological effects of Ca 2+ binding protein modulators on cardiac myofibrillar ATPase activity are dependent upon specied and/or pathological state. it is possible to directly enhance a pathological consequence of cardiac myopathy, depression in maximum MgATPase activity, with pharmacological agents.
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