ALTERED CONTRACTILE FUNCTION IN SLOW-TWITCH MUSCLE FROM TRANSGENIC MICE OVEREXPRESSING PARVALBUMIN

Abstract

827 The purpose of this study was to determine if overexpression of the Ca2+ binding protein, parvalbumin (PV), would lead to alterations in muscle contractile function and induce changes in muscle fiber-type. Two independent lines of transgenic (Tg) mice were generated with a rat PV cDNA driven by the human troponin I slow promoter which directed overexpression of PV specifically in slow (type I) fibers. In non-transgenic wild-type (Wt) littermates, PV expression in slow-twitch soleus muscle was 5% of that in the fast-twitch plantaris muscle. In Tg mice, PV expression in soleus was increased to 40-60% of that in plantaris muscle. Maximum twitch and tetanic tensions did not differ in soleus from Wt vs. Tg (n=8) but there was a rightward shift of the force-frequency curve for Tg soleus. Time to peak tension (TPT) and half-relaxation time (1/2 RT) were significantly decreased in soleus from Tg vs. Wt mice (TPT: 31 ± 1 vs. 41 ± 2 ms, p<0.05; 1/2 RT: 35 ± 2 vs. 45 ± 3 ms, p<0.05, respectively; n=4). The reduction in half-relaxation time is consistent with the role of PV in buffering cytosolic Ca2+ during muscle relaxation. Muscle fiber type, as assessed by myosin ATPase staining, was not different in Tg vs. Wt soleus suggesting that myosin heavy chain expression was not altered. There were no major changes in the expression of myoglobin, GAPDH and phospholamban assessed by reverse transcriptase polymerase chain reaction and normalized to actin expression in Tg vs. Wt soleus. These data show changes in contractile function due to alterations in Ca2+ handling without changes in myosin heavy chain or other selected markers of fiber-type specific gene expression.