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第5回COE(自己組織系物理)セミナー (通算10回)

“Viscous damping of titin elastic recoil in cardiac myofibrils. The role of actin-titin interactions”
講 師 Wolfgang A. Linke
(Physiology and Biophysics Lab., University of Muenster, Schlossplatz 5, D-48149 Muenster, Germany)
日 時 2004年11月17日(水) 15:00-16:00
場 所 早稲田大学理工学部55号館N棟大会議室
講演の概要  The giant protein titin acts as a molecular spring in muscle and contributes greatly to myocardial passive tension. Because the titin spring is extended during diastolic stretch, it will recoil elastically during systole and potentially may influence the overall shortening behavior of cardiac muscle. Here titin elastic recoil was quantified in single human heart myofibrils by using a high-speed (1 kHz) CCD-line camera and a nanonewton-range force sensor. Application of a novel slack-test protocol revealed that the passive shortening velocity (Vp) of stretched cardiomyofibrils depends on: (i) initial sarcomere length, (ii) release-step amplitude, and (iii) temperature. Myofibrillar elastic recoil was very fast initially but slowed down in a near-exponential manner with time constants of a few milliseconds. Selective digestion of titin with low doses of trypsin decelerated the passive recoil and eventually stopped it. Selective extraction of actin filaments with a Ca2+-independent gelsolin fragment greatly reduced the dependency of Vp on release-step size and temperature-due to lowered viscous resistance. Thus, Vp is determined by two factors, titin recoil and internal viscous drag. The recoil could be modeled as that of a damped entropic spring consisting of independent wormlike chains. The viscous damping results mainly from weak actin-titin interactions, since viscous forces were apparent in cardiac myofibrils stretched rapidly both at normal sarcomere length and beyond actin-myosin overlap. The actin-titin interactions involve titin's PEVK domain, as shown by a slow-down of actin-filament sliding over myosin (HMM) molecules in the in-vitro motility assay, in the presence of recombinant PEVK-titin. Other cloned titin constructs did not alter actin-filament sliding in this assay. We conclude that viscous damping of titin elastic recoil may be useful to smooth out sarcomere movements during passive stretch and contraction and to slow down active contraction at the end of systole. Myofibrillar elastic recoil, on the other hand, could help accelerate active contractile speed during early systolic shortening and might also play a role in early diastolic suction to aid ventricular filling.



第6回COE(自己組織系物理)セミナー (通算11回)

“Regulation of oscillatory contraction in insect flight muscle”
講 師 Belinda Bullard
(European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany)
日 時 2004年11月17日(水) 16:00-17:00
場 所 早稲田大学理工学部55号館N棟大会議室
講演の概要  The wingbeat frequencies of small insects can be up to 1000 Hz, which is too fast for individual contractions in the flight muscles to be activated by changes in calcium concentration. The wings, cuticle and flight muscle form a resonant system with an optimum oscillation frequency that depends on the size of the insect. Two opposing sets of flight muscles move the wings up or down; the muscles are activated by periodic stretches and one set of muscles activates the other by stretching it. Oscillatory contraction of flight muscle needs a constant low concentration of calcium. Flight muscle can also be activated by higher concentrations of calcium without stretching, producing an isometric contraction. Regulation works through the troponin complex on muscle thin filaments. In flight muscle, there are two isoforms of the calcium-binding subunit of troponin, TnC. Stretch activation during oscillatory contraction acts on a TnC that has no exchangeable calcium (F1). Isometric contraction is activated by a TnC that has one exchangeable calcium (F2). By replacing the existing TnC with F1 or F2, we show that fibres do oscillatory work with F1 and not F2. The work done by intact fibres depends on the calcium concentration and is the result of activation by both forms of TnC. Stretch and calcium probably act independently on different troponin complexes to control thin filament activation. In this way, the optimum frequency and amplitude of oscillation can be regulated by small changes in calcium concentration.

References:
Pringle, JWS (1978) Stretch activation of muscle: function and mechanism. Proc. Roy Soc. London B 201, 107-130.
Agianian, B, Krzic, U, Qiu, F, Linke, WA, Leonard, K and Bullard, B (2004) A troponin switch that regulates muscle contraction by stretch instead of calcium. EMBO J. 23, 772-779.



















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