Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/82094
Title: Revisiting Frank-Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length-dependent fashion
Authors: Toepfer, Christopher N.
West, Timothy G.
Ferenczi, Michael Alan
Keywords: Cardiac
Regulatory light chain
Issue Date: 2016
Source: Toepfer, C. N., West, T. G., & Ferenczi, M. A. (2016). Revisiting Frank-Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length-dependent fashion. The Journal of Physiology, in press.
Series/Report no.: The Journal of Physiology
Abstract: Force and power in cardiac muscle have a known dependence on phosphorylation of the myosin-associated regulatory light chain (RLC). We explore the effect of RLC phosphorylation on the ability of cardiac preparations to redevelop force (ktr ) in maximally activating [Ca2+ ]. Activation was achieved by rapidly increasing the temperature (temperature-jump of 0.5-20ºC) of permeabilized trabeculae over a physiological range of sarcomere lengths (1.85-1.94 μm). The trabeculae were subjected to shortening ramps over a range of velocities and the extent of RLC phosphorylation was varied. The latter was achieved using an RLC-exchange technique, which avoids changes in the phosphorylation level of other proteins. The results show that increasing RLC phosphorylation by 50% accelerates ktr by ∼50%, irrespective of the sarcomere length, whereas decreasing phosphorylation by 30% slows ktr by ∼50%, relative to the ktr obtained for in vivo phosphorylation. Clearly, phosphorylation affects the magnitude of ktr following step shortening or ramp shortening. Using a two-state model, we explore the effect of RLC phosphorylation on the kinetics of force development, which proposes that phosphorylation affects the kinetics of both attachment and detachment of cross-bridges. In summary, RLC phosphorylation affects the rate and extent of force redevelopment. These findings were obtained in maximally activated muscle at saturating [Ca2+ ] and are not explained by changes in the Ca2+ -sensitivity of acto-myosin interactions. The length-dependence of the rate of force redevelopment, together with the modulation by the state of RLC phosphorylation, suggests that these effects play a role in the Frank-Starling law of the heart.
URI: https://hdl.handle.net/10356/82094
http://hdl.handle.net/10220/41034
ISSN: 0022-3751
DOI: 10.1113/JP272441
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2016 Wellcome Trust The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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