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Regulation of human heart contractility by essential myosin light chain isoforms

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Item Type:Article
Title:Regulation of human heart contractility by essential myosin light chain isoforms
Creators Name:Morano, M. and Zacharzowski, U. and Maier, M. and Lange, P.E. and Alexi-Meskishvili, V. and Haase, H. and Morano, I.
Abstract:Most of the patients with congenital heart diseases express the atrial myosin light chain 1 (ALC-1) in the right ventricle. We investigated the functional consequences of ALC-1 expression on the myosin cycling kinetics in the intact sarcomeric structure using multicellular demembranated fibers ("skinned fibers") from the right ventricular infundibulum of patients with Tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and infundibular pulmonary stenosis (IPS), Force-velocity relation was analyzed by the constant-load technique at maximal Ca2+ activation (pCa 4.5). Half-time of tension development (t1/2) was investigated by monitoring contraction initiation upon photolytic release of ATP from caged-ATP in rigor. The patients investigated here expressed between 0 and 27% ALC-1. There was a statistically significant correlation between ALC-l and maximal shortening velocity (Vmax) which rose 1.87-fold from 1.2 muscle length per second (ML/s) to 2.25 ML/s in a normal (0% ALC-1) and diseased (19.9% ALC-1) ventricle. Half-time of tension development decreased 1.85-fold with increasing ALC-1 expression (t1/2) was 0.252 s and 0.136 s at 2 and 18.4% ALC-1, respectively). We conclude that the expression of ALC-1 in the human heart modulates cross-bridge cycling kinetics accelerating shortening velocity and isometric tension production.
Keywords:Adenosine Triphosphate, Blood Pressure, Calcium, Congenital Heart Defects, Heart, Heart Ventricles, Homeostasis, Kinetics, Myocardial Contraction, Myosin Light Chains, Pulmonary Artery, Pulmonary Valve Stenosis, Reference Values, Tetralogy of Fallot, Vascular Smooth Muscle
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Volume:98
Number:2
Page Range:467-473
Date:15 July 1996
Official Publication:https://doi.org/10.1172/JCI118813
PubMed:View item in PubMed

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