Effects of deletion of muscle LIM protein on myocyte function.

Abstract

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.

• Authors: Z Su, A Yao, I Zubair, K Sugishita, M Ritter, F Li, J J Hunter, K R Chien, W H Barry
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 280 Issue 6 Pg. H2665-73 (Jun 2001) ISSN: 0363-6135 [Print] United States
• PMID: 11356623 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channels, L-Type
• Enzyme Inhibitors
• Fluorescent Dyes
• LIM Domain Proteins
• Muscle Proteins
• Sodium-Calcium Exchanger
• cysteine and glycine-rich protein 3
• diacetylmonoxime
• Diacetyl
• Calcium

Topics

• Actin Cytoskeleton (pathology)
• Animals
• Body Weight
• Calcium (metabolism)
• Calcium Channels, L-Type (metabolism)
• Cardiomyopathy, Dilated (genetics, metabolism, physiopathology)
• Cell Membrane Permeability
• Cell Separation
• Cytoskeleton (metabolism, pathology)
• Diacetyl (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Fluorescent Dyes
• Heart Ventricles (drug effects, metabolism, pathology)
• LIM Domain Proteins
• Mice
• Mice, Knockout
• Muscle Proteins (deficiency, genetics, metabolism)
• Myocardial Contraction
• Myocardium (metabolism, pathology)
• Organ Size
• Patch-Clamp Techniques
• Sarcolemma (metabolism)
• Sarcoplasmic Reticulum (metabolism)
• Sodium-Calcium Exchanger (metabolism)