Effects of myosin heavy chain isoform switching on Ca2+-activated tension development in single adult cardiac myocytes

Cardiac myosin heavy chain (MHC) isoforms are known to play a key role in d efining the dynamic contractile behavior of the heart during development. I t remains unclear, however, whether cardiac MHC isoforms influence other im portant features of cardiac contractility, including the Ca2+ sensitivity o f isometric tension development. To address this question, adult rats were treated chemically to induce the hypothyroid state and cause a transition i n the ventricular cardiac MHC isoform expression pattern from predominantly the alpha-MHC isoform to exclusively the beta-MHC isoform. We found a sign ificant desensitization in the Ca2+ sensitivity of tension development in b eta-MHC-expressing ventricular myocytes (pCa(50)=5.51+/-0.03, where pCa is -log[Ca2+], and pCa(50) is pCa at which tension is one-half maximal) compar ed with that: in predominantly alpha-MHC-expressing myocytes (pCa(50)=5.68/-0.05). No differences between the 2 groups were observed in the steepness of the tension-pCa relationship or in the maximum isometric force generate d. Instantaneous stiffness measurements were made that provide a relative m easure of changes in the numbers of myosin crossbridges attached to actin d uring Ca2+ activation. Results showed that the relative stiffness-pCa relat ionship was shifted to the right in beta-MHC-expressing myocytes compared w ith the alpha-MHC-expressing cardiac myocytes (pCa(50)=5.47+/-0.05 versus 5 .76+/-0.05, respectively). We conclude that MHC isoform switching in adult cardiac myocytes alters the Ca2+ sensitivity of stiffness and tension devel opment. These results suggest that the activation properties of the thin fi lament are in part MHC isoform dependent in cardiac muscle, indicating an a dditional role for MHC isoforms in defining cardiac contractile function.