REGULATION OF HUMAN HEART CONTRACTILITY BY ESSENTIAL MYOSIN LIGHT-CHAIN ISOFORMS

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 dememb ranated fibers (''skinned fibers'') from the right ventricular infundi bulum of patients with Tetralogy of Fallot (TOF), double outlet right ventricle (DORV), and infundibular pulmonary stenosis (IPS). Force-vel ocity relation was analyzed by the constant-load technique at maximal Ca2+ activation (pCa 4.5). Half-time of tension develoment (t(1/2)) wa s investigated by monitoring contraction initiation upon photolytic re lease of ATP from caged-ATP in rigor. The patients investigated here e xpressed between 0 and 27% ALC-1. There was a statistically significan t correlation between ALC-1 and maximal shortening velocity (V-max) wh ich 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. Halfti me of tension development decreased 1.85-fold with increasing ALC-1 ex pression (t(1/2) was 0.252 s and 0.136 s at 2 and 18.4% ALC-1, respect ively). We conclude that the expression of ALC-1 in the human heart mo dulates crossbridge cycling kinetics accelerating shortening velocity and isometric tension production.