Cardiac actin changes in the actomyosin interface have different effects on myosin duty ratio.

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease (CD) that commonly causes an increased size of cardiomyocytes in the left ventricle. The proteins myosin and actin interact in the myocardium to produce contraction through the actomyosin ATPase cycle. The duty ratio (r) of myosin is the proportion of the actomyosin ATPase cycle that myosin is bound to actin and does work. A common hypothesis is that HCM mutations increase contraction in cardiac sarcomeres; however, the available data are not clear on this connection. Based on previous work with human α-cardiac actin (ACTC), we hypothesize that HCM-linked ACTC variants with alterations near the myosin binding site have an increased r, producing more force. Myosin duty ratios using human ACTC variant proteins were calculated with myosin ATPase activity and in-vitro motility data. We found no consistent changes in the duty ratio of the ACTC variants, suggesting that other factors are involved in the development of HCM when ACTC variants are present.