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Crossbridge Scheme and the Kinetic Constants of Elementary Steps Deduced From Chemically Skinned Papillary and Trabecular Muscles of the Ferret
Journal article   Open access   Peer reviewed

Crossbridge Scheme and the Kinetic Constants of Elementary Steps Deduced From Chemically Skinned Papillary and Trabecular Muscles of the Ferret

Masataka Kawai, Yasutake Saeki and Yan Zhao
Circulation research, Vol.73(1), pp.35-50
07/1993
DOI: 10.1161/01.RES.73.1.35
PMID: 8508533
url
https://doi.org/10.1161/01.RES.73.1.35View
Published (Version of record) Open Access

Abstract

(Equation is included in full-text article.)where A is actin, M is myosin, D is MgADP, and Det includes all detached states (MS and MDP) and weakly attached states (AMS and AMDP). From our studies, we obtained K1a=0.99 mM (MgATP association), k1b=270 s (ATP isomerization), k−1b=280 s (reverse isomerization), K1b=k1b/k−1b=0.95, k2=48 s (crossbridge detachment), k−2=14 s (reverse detachment), K2=3.5, k4=11 s (crossbridge attachment), k−4=107 s (reverse attachment), K4=0.11, and K5=0.06 mM (Pi association). k6 is the rate-limiting step, and it is the slowest forward reaction in the cycle, which results in the rigorlike AM state. K1a (MgATP binding) is four times that of rabbit psoas, and K5 (Pi binding) is 0.3 times that of psoas, demonstrating that crossbridges in myocardium bind MgATP more and Pi less than psoas. The rate constants of ATP isomerization (k1b, k−1b), crossbridge detachment (k2, k−2), and crossbridge attachment (k4) steps are generally an order of magnitude slower than rabbit psoas. The reverse attachment step (k−4) is similar to that in psoas, indicating that this step may occur irrespective of the myosin type and possibly spontaneously. The above scheme with the deduced kinetic constants predicts the following crossbridge distributions at 5 mM MgATP and 8 mM PiAM (3%), AM†S (15%), AMS (14%), Det (50%), AMDP (6%), and AMD (12%). The actual number of attached crossbridges was measured to be 51±4% by the stiffness ratio during activation and after rigor induction, and a strong correlation was seen with the prediction. Our results are consistent with the hypothesis that force generation occurs at the Det→AMDPi transition, and the same force is maintained after the release of Pi.

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