ALPHA-SKELETAL ACTIN IS ASSOCIATED WITH INCREASED CONTRACTILITY IN THE MOUSE HEART

BALB/c mice express abnormally high levels of alpha-skeletal actin in the heart, which may be related to a duplication in the promoter of th e alpha-cardiac actin gene. To evaluate the effects of overexpression of the alpha-skeletal actin isoform on cardiac contractile function, w e studied these mice using the isolated perfused work-performing murin e heart model and measured actin isoform expression in the same hearts . We quantified myocardial contractility from the maximum rate of cont raction (+dP/dt) and time to peak pressure and relaxation from -dP/dt and time to half relaxation of left intraventricular pressure. Dot blo ts of total RNA hybridized against oligonucleotide sequences specific for either alpha-skeletal or alpha-cardiac actin mRNA showed that incr eased levels of alpha-skeletal actin RNA correlated significantly with increased contractility of hearts from the BALB/c mice (r=.80, n=15, P<.001). The present study demonstrates a significant functional corre lation between alpha-actin isoform content and cardiac contractile fun ction and also that alpha-skeletal actin may promote an increased cont ractile function in the heart compared with alpha-cardiac actin.