M. Morano et al., REGULATION OF HUMAN HEART CONTRACTILITY BY ESSENTIAL MYOSIN LIGHT-CHAIN ISOFORMS, The Journal of clinical investigation, 98(2), 1996, pp. 467-473
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.