Protein kinase A treatment of wild-type myocardium increased the equatorial intensity ratio I(11)/I(10) from 0.22 to 0.33, indicating increased proximity of myosin heads to actin.
Does PKA treatment alter cross-bridge disposition and lattice spacing in wild-type versus cMyBP-C null mouse myocardium?
PKA phosphorylation of cMyBP-C relieves the tethering of cross-bridges, increasing their proximity to actin and the probability of interaction during contraction.
Tasa de eventos absoluta: 0.33% vs 0.22%
Protein kinase A-mediated (PKA) phosphorylation of cardiac myosin binding protein C (cMyBP-C) accelerates the kinetics of cross-bridge cycling and may relieve the tether-like constraint of myosin heads imposed by cMyBP-C. We favor a mechanism in which cMyBP-C modulates cross-bridge cycling kinetics by regulating the proximity and interaction of myosin and actin. To test this idea, we used synchrotron low-angle x-ray diffraction to measure interthick filament lattice spacing and the equatorial intensity ratio, I(11)/I(10), in skinned trabeculae isolated from wild-type and cMyBP-C null (cMyBP-C(-/-)) mice. In wild-type myocardium, PKA treatment appeared to result in radial or azimuthal displacement of cross-bridges away from the thick filaments as indicated by an increase (approximately 50%) in I(11)/I(10) (0.22+/-0.03 versus 0.33+/-0.03). Conversely, PKA treatment did not affect cross-bridge disposition in mice lacking cMyBP-C, because there was no difference in I(11)/I(10) between untreated and PKA-treated cMyBP-C(-/-) myocardium (0.40+/-0.06 versus 0.42+/-0.05). Although lattice spacing did not change after treatment in wild-type (45.68+/-0.84 nm versus 45.64+/-0.64 nm), treatment of cMyBP-C(-/-) myocardium increased lattice spacing (46.80+/-0.92 nm versus 49.61+/-0.59 nm). This result is consistent with the idea that the myofilament lattice expands after PKA phosphorylation of cardiac troponin I, and when present, cMyBP-C, may stabilize the lattice. These data support our hypothesis that tethering of cross-bridges by cMyBP-C is relieved by phosphorylation of PKA sites in cMyBP-C, thereby increasing the proximity of cross-bridges to actin and increasing the probability of interaction with actin on contraction.
Colson et al. (Fri,) conducted a other in Resting myocardium mechanics. Protein kinase A (PKA) treatment vs. Untreated myocardium was evaluated on Equatorial intensity ratio, I(11)/I(10) in wild-type myocardium. Protein kinase A treatment of wild-type myocardium increased the equatorial intensity ratio I(11)/I(10) from 0.22 to 0.33, indicating increased proximity of myosin heads to actin.
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