title: Isometric force kinetics upon rapid activation and relaxation of mouse, guinea pig and human heart muscle studied on the subcellular myofibrillar level.
abstract: The kinetics of force development and relaxation upon rapid application and removal of Ca2+ was measured in bundles of few myofibrils isolated from triton X-100 skinned left ventricular trabeculae of mice (M), guinea pigs (G) and humans (H). Upon rapidly switching from relaxing solution (pCa 7.5) to activating solution (pCa 4.5) at 10 degrees C, force rose by a single exponential with a rate constant k(act) of 5.2 s(-1) (M), 1.7 s(-1) (G) and 0.3 s(-1) (H) to a plateau of 0.14 microN/microm2 (M), 0.16 microN/microm2 (G) and 0.15 microN/microm2 (H). A rapid release followed by a rapid restretch to the original length applied during steady-state Ca2+ activation at pCa 4.5 induced an exponential force redevelopment with a rate constant k(redev) that was indistinguishable from k(act), indicating that k(act) is limited by cross-bridge turnover kinetics rather than by the Ca2+-induced activation of the regulatory system. Upon rapidly switching from pCa 4.5 to pCa 7.5, force decayed in a pronounced biphasic manner. Thus a slow initial, almost linear decay with a rate constant k(lin) of 1.8 s(-1) (M), 0.6 s(-1) (G) and 0.15 s(-1) (H) and a duration t(lin) of 0.06 s (M), 0.11 s (G) and 0.3 s (H) was followed by a rapid exponential decay with a rate constant k(rel) of 18 s(-1) (M), 11 s(-1) (G) and 4.6 s(-1) (H). The pronounced biphasic shapes of the force decays determined here for the first time in cardiac myofibrils differs from the force decays that had been reported for multicellular skinned trabeculae in which relaxation was induced by rapid removal of Ca2+ by flash photolysis of caged Ca2+ chelators. In the skinned trabeculae, no pronounced initial slow phase was observed. The force decays shown here are much more similar to those reported for single skeletal myofibrils. The kinetics of isometric relaxation of skinned trabeculae (i.e., multicellular preparations), therefore, do not reflect the kinetics of force relaxation at the cardiac myofibrillar level.
authors.affiliation: Institute of Physiology, Universität zu Köln, Robert-Koch-Str. 39, 50931 Köln, Germany. Robert.Stehle@Uni-Koeln.de
authors.forename: Robert
authors.initials: R
authors.lastname: Stehle
authors.forename: Martina
authors.initials: M
authors.lastname: Krüger
authors.forename: Peter
authors.initials: P
authors.lastname: Scherer
authors.forename: Klara
authors.initials: K
authors.lastname: Brixius
authors.forename: Robert H G
authors.initials: RH
authors.lastname: Schwinger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfitzer
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007700:Kinetics; D051379:Mice; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology*; D013347:Subcellular Fractions / Q000502:physiology; D013696:Temperature
chemical_list: D002021:Buffers; D002118:Calcium