Overexpression of SERCA2a protein results in a positive inotropic effect under baseline conditions remaining preserved under pressure overload without affecting mortality. Therefore therapeutic transfer of SERCA2a may become a potential approach for gene therapy of congestive heart failure. Moreover, transgenic SERCA2a rats will be useful for studies of long-term SERCA2a overexpression in further cardiovascular disease models.

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Nitrate uptake was followed continuously in cultures of Chlorella sorokiniana using ionsensitive electrodes. During the lifecycle of the synchronous cell cultures, a drastic increase occurred in the first hour after the onset of the light. Nitrate uptake rate was shown to be dependent on illumination intensity, nitrate concentration, and temperature. These results point to an energy-linked uptake process. From the different timecourses of nitrate uptake rate and nitrate reductase activation, one can conclude that the increased nitrate reductase activity after light onset is regulated via nitrate uptake. Further evidence for a regulation in this direction is shown by the action of ammonium on nitrate uptake and nitrate reductase activity. The results are discussed in terms of the regulation of the nitrate consuming system.

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Although it is established that familial hypertrophic cardiomyopathy (FHC) is caused by mutations in several sarcomeric proteins, including cardiac troponin T (TnT), its pathogenesis is still not completely understood. Previously, we established a transgenic rat model of FHC expressing a human TnT molecule with a truncation mutation (DEL-TnT). This study investigated whether contractile dysfunction and electrical vulnerability observed in DEL-TnT rats might be due to alterations of intracellular Ca 2؉ homeostasis, myofibrillar Ca 2؉ sensitivity, and/or myofibrillar ATP utilization. Simultaneous measurements of the force of contraction and intracellular Ca 2؉ transients were performed in right ventricular trabeculae of DEL-TnT hearts at 0.25 and 1.0 Hz. Rats expressing wild-type human TnT as well as nontransgenic rats served as controls. In addition, calcium-dependent ATPase activity and tension development were investigated in skinned cardiac muscle fibers. Force of contraction was significantly decreased in DEL-TnT compared with nontransgenic rats and TnT. Time parameters of Ca 2؉ transients were unchanged at 0.25 Hz but prolonged at 1.0 Hz in DEL-TnT. The amplitude of the fura-2 transient was similar in all groups investigated, whereas diastolic and systolic fura-2 ratios were found elevated in rats expressing nontruncated human troponin T. In DEL-TnT rats, myofibrillar Ca 2؉ -dependent tension development as well as Ca 2؉ sensitivity of tension were significantly decreased, whereas tension-dependent ATP consumption ("tension cost") was markedly increased. Thus, a C-terminal truncation of the cardiac TnT molecule impairs the force-generating capacity of the cycling cross-bridges resulting in increased tension-dependent ATP utilization. Taken together, our data support the hypothesis of energy compromise as a contributing factor in the pathogenesis of FHC. Familial hypertrophic cardiomyopathy (FHC)3 is an autosomal-dominant inherited disease characterized by ventricular hypertrophy, arrhythmias, and sudden death. The phenotype of affected individuals may vary from early sudden death, marked hypertrophy with contractile dysfunction, to an asymptomatic carrier status (reviewed in Refs. 1-3). In the past 10 years, several genes could be linked to FHC, almost uniformly encoding contractile proteins such as ␤-myosin heavy chain and cardiac troponin T (4). FHC has thus been labeled a "disease of the sarcomere" (5). Mutations of the cardiac troponin T (cTnT) gene are of particular interest because they are associated with a high incidence of arrhythmias and sudden death even in the absence of significant myocardial hypertrophy (6). Yet the pathogenesis of FHC is still poorly understood, and there is no clear understanding how these mutations lead to the development of FHC with diastolic dysfunction and sudden cardiac death. Biochemical and biophysical analyses have failed to identify a common mechanism underlying the alterations of cardiac contractility resulting from these mutations. For example, missense mutations i...

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