z-logo
open-access-imgOpen Access
cMyBP-C phosphorylation modulates the time-dependent slowing of unloaded shortening in murine skinned myocardium
Author(s) -
Jasmine Giles,
Daniel P. Fitzsimons,
Jitandrakumar R. Patel,
Chloe Knudtsen,
Alexander Neuville,
Richard L. Moss
Publication year - 2021
Publication title -
the journal of general physiology/the journal of general physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.064
H-Index - 127
eISSN - 1540-7748
pISSN - 0022-1295
DOI - 10.1085/jgp.202012782
Subject(s) - phosphorylation , actin , myosin , biophysics , protein kinase a , cardiac muscle , chemistry , kinase , medicine , biology , microbiology and biotechnology , endocrinology
In myocardium, phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) is thought to modulate the cooperative activation of the thin filament by binding to myosin and/or actin, thereby regulating the probability of cross-bridge binding to actin. At low levels of Ca2+ activation, unloaded shortening velocity (Vo) in permeabilized cardiac muscle is comprised of an initial high-velocity phase and a subsequent low-velocity phase. The velocities in these phases scale with the level of activation, culminating in a single high-velocity phase (Vmax) at saturating Ca2+. To test the idea that cMyBP-C phosphorylation contributes to the activation dependence of Vo, we measured Vo before and following treatment with protein kinase A (PKA) in skinned trabecula isolated from mice expressing either wild-type cMyBP-C (tWT), nonphosphorylatable cMyBP-C (t3SA), or phosphomimetic cMyBP-C (t3SD). During maximal Ca2+ activation, Vmax was monophasic and not significantly different between the three groups. Although biphasic shortening was observed in all three groups at half-maximal activation under control conditions, the high- and low-velocity phases were faster in the t3SD myocardium compared with values obtained in either tWT or t3SA myocardium. Treatment with PKA significantly accelerated both the high- and low-velocity phases in tWT myocardium but had no effect on Vo in either the t3SD or t3SA myocardium. These results can be explained in terms of a model in which the level of cMyBP-C phosphorylation modulates the extent and rate of cooperative spread of myosin binding to actin.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here