Myostatin represses physiological hypertrophy of the heart and excitation–contraction coupling
AUTOR(ES)
Rodgers, Buel D
FONTE
Blackwell Science Inc
RESUMO
Although myostatin negatively regulates skeletal muscle growth, its function in heart is virtually unknown. Herein we demonstrate that it inhibits basal and IGF-stimulated proliferation and differentiation and also modulates cardiac excitation–contraction (EC) coupling. Loss of myostatin induced eccentric hypertrophy and enhanced cardiac responsiveness to β-adrenergic stimulation in vivo. This was due to myostatin null ventricular myocytes having larger [Ca2+]i transients and contractions and responding more strongly to β-adrenergic stimulation than wild-type cells. Enhanced cardiac output and β-adrenergic responsiveness of myostatin null mice was therefore due to increased SR Ca2+ release during EC coupling and to physiological hypertrophy, but not to enhanced myofilament function as determined by simultaneous measurement of force and ATPase activity. Our studies support the novel concept that myostatin is a repressor of physiological cardiac muscle growth and function. Thus, the controlled inhibition of myostatin action could potentially help repair damaged cardiac muscle by inducing physiological hypertrophy.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2770153Documentos Relacionados
- CaMKIIdelta overexpression in hypertrophy and heart failure: cellular consequences for excitation-contraction coupling
- Local control of excitation-contraction coupling in rat heart cells.
- Optical studies of excitation-contraction coupling in the early embryonic chick heart.
- A PRELIMINARY NOTE ON EXCITATION-CONTRACTION COUPLING
- Valinomycin and excitation-contraction coupling in skeletal muscle fibres of the frog.