Comparison of Unitary Displacements and Forces Between 2 Cardiac Myosin Isoforms by the Optical Trap Technique

Molecular Basis for Cardiac Adaptation

From The Second Department of Internal Medicine, School of Medicine, University of Tokyo (S.S., N.K., H.F., H.Y., S.M., M.O.), and the Department of Physiology, Teikyo University, School of Medicine (S.C., H.S.), Tokyo, Japan.

Correspondence to Seiryo Sugiura, MD, The 2nd Department of Internal Medicine, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. E-mail Sugiura-2IM{at}h.u.-tokyo.ac.jp

Abstract—To provide information on the mechanism of cardiac adaptation at the molecular level, we compared the unitary displacements and forces between the 2 rat cardiac myosin isoforms, V₁ and V₃. A fluorescently labeled actin filament, with a polystyrene bead attached, was caught by an optical trap and brought close to a glass surface sparsely coated with either of the 2 isoforms, so that the actin-myosin interaction took place in the presence of a low concentration of ATP (0.5 µmol/L). Discrete displacement events were recorded with a low trap stiffness (0.03 to 0.06 pN/nm). Frequency distribution of the amplitude of the displacements consisted of 2 gaussian curves with peaks at 9 to 10 and 18 to 20 nm for both V₁ and V₃, suggesting that 9 to 10 nm is the unitary displacement for both isoforms. The duration of the displacement events was longer for V₃ than for V₁. On the other hand, discrete force transients were recorded with a high trap stiffness (2.1 pN/nm), and their amplitude showed a broad distribution with mean values between 1 and 2 pN for V₁ and V₃. The durations of the force transients were also longer for V₃ than for V₁. These results indicate that both the unitary displacements and forces are similar in amplitude but different in duration between the 2 cardiac myosin isoforms, being consistent with the reports that the tension cost is higher in muscles consisting mainly of V₁ than those consisting mainly of V₃.

Key Words: cardiac myosin • unitary displacement • unitary force • laser optical trap

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