Deletion of muscle LIM protein in mice led to significantly increased peak systolic intracellular Ca2+ (603 vs 349 nM) and diminished fractional shortening despite normal or enhanced SR Ca2+ function.
Does deletion of muscle LIM protein alter myocyte contractility and calcium handling in mice?
Deletion of muscle LIM protein in mice leads to depressed contractility due to reduced Ca2+-induced shortening and myofibril disorganization, despite normal or enhanced SR Ca2+ handling.
Absolute Event Rate: 603% vs 349%
Muscle LIM protein (MLP) may serve as a scaffold protein on the actin-based cytoskeleton, and mice deficient in this protein (MLPKO) have been recently reported to develop dilated cardiomyopathy. To determine the causes of depressed contractility in this model, we measured intracellular Ca2+ concentration (Ca2+i) transients (fluo 3), cell shortening, L-type Ca2+ channel current (I(Ca,L)), Na/Ca exchanger current (I(Na/Ca)), and sarcoplasmic reticulum (SR) Ca content in left ventricular MLPKO myocytes. I(Ca,L)-voltage relationships, I(Na/Ca) density, and membrane capacitance did not differ between wild-type (WT) and MLPKO myocytes. The peak systolic Ca2+i was significantly increased in MLPKO myocytes (603 +/- 54 vs. 349 +/- 18 nM in WT myocytes). The decline of Ca2+i transients was accelerated in MLPKO myocytes, and SR Ca2+ content was increased by 21%, indicating that SR Ca2+-ATPase function is normal or enhanced in MLPKO myocytes. Confocal imaging of actin filaments stained with tetramethylrhodamine isothiocyanate-labeled phalloidin showed disorganization of myofibrils and abnormal alignment of Z bands, and fractional shortening was significantly diminished in MLPKO myocytes compared with that in WT myocytes at comparable peak Ca2+i. Thus a reduced Ca2+-induced shortening may be involved in the pathogenesis of myocardial dysfunction in this genetic model of heart failure.
Su et al. (Fri,) conducted a other in Dilated cardiomyopathy. Deletion of muscle LIM protein (MLPKO) vs. Wild-type (WT) was evaluated on Peak systolic intracellular Ca2+ concentration ([Ca2+]i). Deletion of muscle LIM protein in mice led to significantly increased peak systolic intracellular Ca2+ (603 vs 349 nM) and diminished fractional shortening despite normal or enhanced SR Ca2+ function.