Alterations of mechanical parameters in chemically skinned preparations of rat myocardium as a function of isoenzyme pattern of myosin

Abstract

Myofibrillar ATPase activity, maximum unloaded shortening velocity, and isometric tension development were evaluated in left ventricular preparations of 5-week-old rats with a high endogeneous level of thyroid hormones and hypothyroid rats after 4-week treatment with propylthiouracil (PTU). The range of possible alterations of the above functional parameters was defined in relation to myosin isoenzyme distribution. The mechanical behaviour of the ventricular preparations was investigated in native myocardium as well as in the glycerinated state. The essential results of the present study is that alterations of myofibrillar ATPase activity and mechanical Vmax, evaluated in glycerinated preparations, are limited to a well-defined range of similar magnitude for both functional parameters: 32-40% of maximum values (obtained from rat myocardium with homogeneous myosin V1). Isometric tension was only insignificantly decreased in glycerinated preparations of the PTU-treated group. The alteration in the apparent maximum shortening velocity of native myocardium (V0) was of the same magnitude as changes in Vmax of chemically skinned preparations. Physical training revealed a shift in the direction of V1-type myosin with increased ATPase activity and shortening velocity; aging and pressure overload showed an opposite effect. The documented mechanical alterations do not contradict an adaptational interpretation of the myosin isoenzyme redistribution in pressure-induced hypertrophy.

Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle.

“…Moreover, hypothyroidism is associated with a great reduction in Vma. (34,35) and AFIs (34,49), which we did not observe in our model.…”

“…Under various physiological and pathological conditions, including development (24) and hormonal (26,28) and chronic hemodynamic alterations (25,(29)(30)(31), the relative proportions of these isomyosins change as a result of modifications in the expression of the corresponding genes (32,33). These changes are well correlated with the alterations in the myocardial performance of the different rat and rabbit models so far studied (34)(35)(36)(37)(38).…”

Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats

“…This completely corresponds to earlier observations that the myosin isoenzyme profile is profoundly affected in hypothyroidism due to downregulation of the ␣-MHC gene that is linked to an increased expression ␤-MHC in both rat and mouse heart (25,29). This molecular switch is known to slow down cardiac contraction (11,17). Note that the found marked increase in ␤-MHC protein levels in hypothyroid hearts did not differ between WT and TG.…”

“…These observations allow us to think that a possible increase in the consumption of ATP due to expression of additional SERCA2a molecules coded by the SERCA2 minigene was obviously not associated with a significant energy deficit in hypothyroid TG hearts. Most probably, this can result from an increased economy of ATP utilization due to both the improvement of cellular Ca 2ϩ handling and slowed cross-bridge cycling of ␤-MHC-rich isomyosins with low ATPase activity (11,17) in the latter animals. Thus it appears that the improvement of SR Ca 2ϩ handling by introducing SERCA2a minigene is an energetically favorable treatment for preventing contractile dysfunction in diseased states.…”

“…Initial rates of SR oxalatesupported Ca uptake were estimated in LV homogenates by a standard procedure (7). The reaction medium contained 40 mM imidazole (pH 7.0), 100 mM KCl, 5 mM MgCl 2, 5 mM Tris-ATP, 6 mM phosphocreatine, 10 mM K-oxalate, 0.2 mM EGTA, 10 mM NaN3, 0.025 to 0.25 mM 45 CaCl2 (1.9 ϫ 10 11 Bq/mol), 2 M synthetic protein kinase A inhibitor peptide [PKI (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)amide] (GIBCO, Life Technologies, Eggenstein, Germany), and 30 g of homogenate protein per 0.2 ml. The free Ca 2ϩ concentration was calculated using Fabiato's computer program as described elsewhere (7).…”