Calcium channel blockade limits transcriptional, translational and functional up-regulation of the cardiac calpain system after XXXX .

@entity296 @entity5988 @entity35 @entity63 @entity1283 @entity946 @entity1188 @entity3591 @entity1562 @entity141 @entity583
Abnormal @entity141 inward current through cardiac @entity141 channels during @entity63 has been shown to be an initial signal for activation of myocardial @entity141 -dependent enzymes. This study investigated the contribution of cardiac L- and T-type @entity141 channels in the calpain-mediated @entity296 following @entity583 . @entity583 was induced by permanent ligation of the left coronary artery. Infarcted @entity35 were orally treated with placebo, @entity3591 (L-channel blockade; 4 mg/kg/day) or mibefradil (L-/T-channel blockade; 10 mg/kg/day) beginning 7 days before induction of @entity583 . Gene expression, protein levels and enzyme activity of calpains I and II were measured 1, 3, 7 and 14 days postcoronary occlusion in the noninfarcted and @entity1188 . Infarct size, @entity5988 and interstitial collagen volume fraction were determined in picrosirius red-stained hearts. @entity583 induced an up-regulation of calpain I mRNA, protein and activity in the noninfarcted @entity1562 (maximum 14 days postinfarction), whereas mRNA, protein and activity of calpain II were maximally increased in the @entity1188 3 days postinfarction. Fourteen days postinfarction, @entity1188 size was 49%, the left ventricle was dilated and interstitial collagen volume fraction was increased. @entity3591 -inhibited mRNA, protein and activity up-regulation of calpain I decreased interstitial collagen volume fraction and @entity1188 size. @entity946 -attenuated mRNA, protein and activity up-regulation of calpain II at all four time points measured and of calpain I at 7 and 14 days postinfarction reduced @entity1188 size and prevented @entity5988 . @entity1188 -induced @entity1283 was accompanied by an up-regulation of calpain I, whereas calpain II was up-regulated in the @entity1188 . Cardiac L- and T-type @entity141 channel blockade differentially reduced postinfarction remodeling associated with selective inhibition of cardiac calpains I and II, respectively.
