Mechanical and energetic properties of papillary muscle from ACTC E99K transgenic mouse models of hypertrophic cardiomyopathy
| Autor: | Weihua Song, Christina Rowlands, Nancy A. Curtin, Steven B. Marston, Roger C. Woledge, Michael A. Ferenczi, Petr G. Vikhorev, Kenneth T. MacLeod, Mavin N Kashyap |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Physiology Transducers Energy metabolism Cardiomegaly Mice Transgenic In Vitro Techniques 030204 cardiovascular system & hematology Biology Mice 03 medical and health sciences 0302 clinical medicine Myofibrils Heart Rate Isometric Contraction Physiology (medical) Internal medicine medicine Animals Myocytes Cardiac Calcium Signaling Papillary muscle Actin 030304 developmental biology 0303 health sciences Hypertrophic cardiomyopathy Thermogenesis Papillary Muscles medicine.disease Myocardial Contraction Electric Stimulation Biomechanical Phenomena Cell biology medicine.anatomical_structure Endocrinology Mutation (genetic algorithm) Energy Metabolism Cardiology and Cardiovascular Medicine Muscle Mechanics and Ventricular Function |
| Zdroj: | AJP: Heart and Circulatory Physiology; Vol 304 AJP: Heart and Circulatory Physiology |
| ISSN: | 0363-6135 |
| DOI: | 10.1152/ajpheart.00951.2012 |
| Popis: | We compared the contractile performance of papillary muscle from a mouse model of hypertrophic cardiomyopathy [α-cardiac actin ( ACTC) E99K mutation] with nontransgenic (non-TG) littermates. In isometric twitches, ACTC E99K papillary muscle produced three to four times greater force than non-TG muscle under the same conditions independent of stimulation frequency and temperature, whereas maximum isometric force in myofibrils from these muscles was not significantly different. ACTC E99K muscle relaxed slower than non-TG muscle in both papillary muscle (1.4×) and myofibrils (1.7×), whereas the rate of force development after stimulation was the same as non-TG muscle for both electrical stimulation in intact muscle and after a Ca2+jump in myofibrils. The EC50for Ca2+activation of force in myofibrils was 0.39 ± 0.33 μmol/l in ACTC E99K myofibrils and 0.80 ± 0.11 μmol/l in non-TG myofibrils. There were no significant differences in the amplitude and time course of the Ca2+transient in myocytes from ACTC E99K and non-TG mice. We conclude that hypercontractility is caused by higher myofibrillar Ca2+sensitivity in ACTC E99K muscles. Measurement of the energy (work + heat) released in actively cycling heart muscle showed that for both genotypes, the amount of energy turnover increased with work done but with decreasing efficiency as energy turnover increased. Thus, ACTC E99K mouse heart muscle produced on average 3.3-fold more work than non-TG muscle, and the cost in terms of energy turnover was disproportionately higher than in non-TG muscles. Efficiency for ACTC E99K muscle was in the range of 11–16% and for non-TG muscle was 15–18%. |
| Databáze: | OpenAIRE |
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