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- W2094090690 abstract "Increased production of oxygen radicals is involved in many cardiac deseases. In a cardiac-specific Rac1-overexpressing mouse line (RacET) NADPH oxidase activity is upregulated 6-7 fold. Here, we characterise ventricular remodelling processes with respect to calcium handling and ion currents in ventricular myocytes. We used 4-6 months old RacET and age-matched wt mice. In ventricular cells of RacET baseline calcium concentrations were significantly decreased. In post-rest behaviour the first amplitude was unchanged but the steady-state amplitude was down to almost 50% of the wt-value. Interestingly, RacET myocytes displayed significantly increased amplitudes of caffeine-induced calcium transients (up by 50%), while Na/Ca-exchange and SERCA-pump activity appeared unchanged. A similar behaviour was observed in cell-length experiments. Here, RacET myocytes displayed a significantly shorter resting cell length (down by 15%), in post-rest behaviour experiments the first twitch amplitude was unchanged while in steady-state their contraction was significantly reduced. When analysing calcium sparks we found that their amplitude was almost doubled in RacET cells while the recovery was speeded up 25%, their spatial spread was reduced by 25% when compared to wt. The membrane capacity of the RacET myocytes was significantly reduced (down by 40%) and action potentials were largely distorted, whereby both upstroke and repolarisation phase were altered. From these data we conclude that RacET overexpression and the accompanying increased oxygen radical load results in ventricular remodelling, even in the absence of hypertrophy.Support by DFG (SFB530, GraKo1320, KliFor196), BfR, BMBF" @default.
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- W2094090690 date "2010-01-01" @default.
- W2094090690 modified "2023-09-29" @default.
- W2094090690 title "Remodelling of Calcium Handling, Ion Currents and Contraction in Rac1 Overexpressing Mouse Ventricle" @default.
- W2094090690 doi "https://doi.org/10.1016/j.bpj.2009.12.2981" @default.
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