Abstract
Myosin binding protein-C (MyBP-C) is localized to the thick filaments of striated muscle where it appears to have both structural and regulatory functions. Importantly, mutations in the cardiac MyBP-C gene are associated with familial hypertrophic cardiomyopathy. The purpose of this study was to examine the role that MyBP-C plays in regulating force, power output, and force development rates in cardiac myocytes. Skinned cardiac myocytes from wild-type (WT) and MyBP-C knockout (MyBP-C-/-) mice were attached between a force transducer and position motor. Force, loaded shortening velocities, and rates of force redevelopment were measured during both maximal and half-maximal Ca2+ activations. Isometric force was not different between the two groups with force being 17.0±7.2 and 20.5±3.1 kN/m2 in wild-type and MyBP-C-/- myocytes, respectively. Peak normalized power output was significantly increased by 26% in MyBP-C-/- myocytes (0.15±0.01 versus 0.19±0.03 P/Po · ML/sec) during maximal Ca2+ activations. Interestingly, peak power output in MyBP-C-/- myocytes was increased to an even greater extent (46%, 0.09±0.03 versus 0.14±0.02 P/Po · ML/sec) during half-maximal Ca2+ activations. There was also an effect on the rate constant of force redevelopment (ktr) during half-maximal Ca2+ activations, with ktr being significantly greater in MyBP-C-/- myocytes (WT=5.8±0.9 s-1 versus MyBP-C-=7.7±1.7 s-1). These results suggest that cMyBP-C is an important regulator of myocardial work capacity whereby MyBP-C acts to limit power output.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 752-758 |
| Number of pages | 7 |
| Journal | Circulation Research |
| Volume | 93 |
| Issue number | 8 |
| DOIs | |
| State | Published - Oct 17 2003 |
| Externally published | Yes |
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Keywords
- Cardiac contractility
- Cardiac myocytes
- Myosin binding protein-C
- Power output
- Sarcomere proteins
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Loaded Shortening, Power Output, and Rate of Force Redevelopment Are Increased With Knockout of Cardiac Myosin Binding Protein-C. / Korte, F. Steven; McDonald, Kerry S.; Harris, Samantha P.; Moss, Richard L.
In: Circulation Research, Vol. 93, No. 8, 17.10.2003, p. 752-758.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loaded Shortening, Power Output, and Rate of Force Redevelopment Are Increased With Knockout of Cardiac Myosin Binding Protein-C
AU - Korte, F. Steven
AU - McDonald, Kerry S.
AU - Harris, Samantha P.
AU - Moss, Richard L.
PY - 2003/10/17
Y1 - 2003/10/17
N2 - Myosin binding protein-C (MyBP-C) is localized to the thick filaments of striated muscle where it appears to have both structural and regulatory functions. Importantly, mutations in the cardiac MyBP-C gene are associated with familial hypertrophic cardiomyopathy. The purpose of this study was to examine the role that MyBP-C plays in regulating force, power output, and force development rates in cardiac myocytes. Skinned cardiac myocytes from wild-type (WT) and MyBP-C knockout (MyBP-C-/-) mice were attached between a force transducer and position motor. Force, loaded shortening velocities, and rates of force redevelopment were measured during both maximal and half-maximal Ca2+ activations. Isometric force was not different between the two groups with force being 17.0±7.2 and 20.5±3.1 kN/m2 in wild-type and MyBP-C-/- myocytes, respectively. Peak normalized power output was significantly increased by 26% in MyBP-C-/- myocytes (0.15±0.01 versus 0.19±0.03 P/Po · ML/sec) during maximal Ca2+ activations. Interestingly, peak power output in MyBP-C-/- myocytes was increased to an even greater extent (46%, 0.09±0.03 versus 0.14±0.02 P/Po · ML/sec) during half-maximal Ca2+ activations. There was also an effect on the rate constant of force redevelopment (ktr) during half-maximal Ca2+ activations, with ktr being significantly greater in MyBP-C-/- myocytes (WT=5.8±0.9 s-1 versus MyBP-C-=7.7±1.7 s-1). These results suggest that cMyBP-C is an important regulator of myocardial work capacity whereby MyBP-C acts to limit power output.
AB - Myosin binding protein-C (MyBP-C) is localized to the thick filaments of striated muscle where it appears to have both structural and regulatory functions. Importantly, mutations in the cardiac MyBP-C gene are associated with familial hypertrophic cardiomyopathy. The purpose of this study was to examine the role that MyBP-C plays in regulating force, power output, and force development rates in cardiac myocytes. Skinned cardiac myocytes from wild-type (WT) and MyBP-C knockout (MyBP-C-/-) mice were attached between a force transducer and position motor. Force, loaded shortening velocities, and rates of force redevelopment were measured during both maximal and half-maximal Ca2+ activations. Isometric force was not different between the two groups with force being 17.0±7.2 and 20.5±3.1 kN/m2 in wild-type and MyBP-C-/- myocytes, respectively. Peak normalized power output was significantly increased by 26% in MyBP-C-/- myocytes (0.15±0.01 versus 0.19±0.03 P/Po · ML/sec) during maximal Ca2+ activations. Interestingly, peak power output in MyBP-C-/- myocytes was increased to an even greater extent (46%, 0.09±0.03 versus 0.14±0.02 P/Po · ML/sec) during half-maximal Ca2+ activations. There was also an effect on the rate constant of force redevelopment (ktr) during half-maximal Ca2+ activations, with ktr being significantly greater in MyBP-C-/- myocytes (WT=5.8±0.9 s-1 versus MyBP-C-=7.7±1.7 s-1). These results suggest that cMyBP-C is an important regulator of myocardial work capacity whereby MyBP-C acts to limit power output.
KW - Cardiac contractility
KW - Cardiac myocytes
KW - Myosin binding protein-C
KW - Power output
KW - Sarcomere proteins
UR - http://www.scopus.com/inward/record.url?scp=0142024741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142024741&partnerID=8YFLogxK
U2 - 10.1161/01.RES.0000096363.85588.9A
DO - 10.1161/01.RES.0000096363.85588.9A
M3 - Article
C2 - 14500336
AN - SCOPUS:0142024741
VL - 93
SP - 752
EP - 758
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 8
ER -