Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C.
The role of cardiac myosin binding protein-C (MyBP-C) on myocardial stiffness was examined in skinned papillary muscles of wild-type (WT(+/+)) and homozygous truncated cardiac MyBP-C (MyBP-C(t/t) male mice. No MyBP-C was detected by gel electrophoresis or by Western blots in the MyBP-C(t/t) myocardium. Rigor-bridge dependent myofilament stiffness, i.e., rigor minus relaxed stiffness, in the MyBP-C(t/t) myocardium (281 +/- 44 kN/m2) was 44% that in WT(+/+) (633 +/- 141 kN/m2). The center-to-center spacing between thick filaments as determined by X-ray diffraction in MyBP-C(t/t) (45.0 +/- 1.2 nm) was not significantly different from that in WT(+/+) (43.2 +/- 0.9 nm). The fraction of cross-sectional area comprised of myofibrils, as determined by electron microscopy, was reduced in the MyBP-C(t/t) (39.9%) by 10% compared to WT(+/+) (44.5%). These data suggest that the 56% reduction in rigor-bridge dependent stiffness of the skinned MyBP-C(t/t) myocardium could not be due solely to a 10% reduction in the number of thick filaments per cross-sectional area and must also be due to approximately 50% reduction in the stiffness of the rigor-bridge attached thick filaments lacking MyBP-C.
Palmer
Bradley M
BM
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA. palmer@physiolocy.med.uvm.edu
McConnell
Bradley K
BK
Li
Guo Hua
GH
Seidman
Christine E
CE
Seidman
J G
JG
Irving
Thomas C
TC
Alpert
Norman R
NR
Maughan
David W
DW
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000648:ultrastructure; D009210:Myofibrils / Q000648:ultrastructure; D010210:Papillary Muscles / Q000502:physiology / Q000648:ultrastructure; D012518:Sarcomeres / Q000648:ultrastructure; D014961:X-Ray Diffraction; D000099163:Myosin Binding Protein C
D002118:Calcium; D002352:Carrier Proteins; D000099163:Myosin Binding Protein C