LENGTH DEPENDENCE OF CA2-C( SENSITIVITY OF TENSION IN MOUSE CARDIAC MYOCYTES EXPRESSING SKELETAL TROPONIN)

1. Beat-to-beat performance of myocardium is highly dependent on sarco mere length. The physiological basis for this effect is not well under stood but presumably includes alterations in the extent of overlap bet ween thick and thin filaments. Sarcomere length dependence of activati on also appears to be involved since length-tension relationships in c ardiac muscle are usually steeper than those in skeletal muscle. 2. An explanation recently proposed to account for the difference between l ength-tension relationships is that the cardiac isoform of troponin C (cTnC) has intrinsic properties that confer greater length-dependent c hanges in the Ca2+ sensitivity of tension than does skeletal troponin C (sTnC), presumably due to greater length-dependent changes in the Ca 2+-binding affinity of cTnC. To test this hypothesis, transgenic mice were developed in which fast sTnC was expressed ectopically in the hea rt. This allowed a comparison of the length dependence of the Ca2+ sen sitivity of tension between myocytes having thin filaments that contai ned either endogenous cTnC or primarily sTnC. 3. In myocytes from both transgenic and normal mice, the Ca2+ sensitivity of tension increased similarly when mean sarcomere length was increased from approximately 1.83 to 2.23 mu m. In both cases, the mid-point (pCa(50)) of the tens ion-pCa (i.e. -log[Ca2+]) relationship shifted 0.12 +/- 0.01 pCa units (mean +/- S.E.M.) in the direction of lower Ca2+. 4. We conclude that the Ca2+ sensitivity of tension in myocytes changes as a function of sarcomere length but is independent of the isoform of troponin C prese nt in the thin filaments.