Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling

Buel D. Rodgers, Jillian P. Interlichia, Dilip K. Garikipati, Ranganath Mamidi, Murali Chandra, O. Lynne Nelson, Charles E. Murry, Luis Fernando Santana

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4873-4886
Number of pages14
JournalJournal of Physiology
Volume587
Issue number20
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Myostatin
Excitation Contraction Coupling
Cardiomegaly
Adrenergic Agents
Hypertrophy
Myocardium
Myofibrils
Growth
Cardiac Output
Muscle Cells
Adenosine Triphosphatases
Skeletal Muscle

ASJC Scopus subject areas

  • Physiology

Cite this

Rodgers, B. D., Interlichia, J. P., Garikipati, D. K., Mamidi, R., Chandra, M., Nelson, O. L., ... Santana, L. F. (2009). Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling. Journal of Physiology, 587(20), 4873-4886. https://doi.org/10.1113/jphysiol.2009.172544

Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling. / Rodgers, Buel D.; Interlichia, Jillian P.; Garikipati, Dilip K.; Mamidi, Ranganath; Chandra, Murali; Nelson, O. Lynne; Murry, Charles E.; Santana, Luis Fernando.

In: Journal of Physiology, Vol. 587, No. 20, 10.2009, p. 4873-4886.

Research output: Contribution to journalArticle

Rodgers, BD, Interlichia, JP, Garikipati, DK, Mamidi, R, Chandra, M, Nelson, OL, Murry, CE & Santana, LF 2009, 'Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling', Journal of Physiology, vol. 587, no. 20, pp. 4873-4886. https://doi.org/10.1113/jphysiol.2009.172544
Rodgers BD, Interlichia JP, Garikipati DK, Mamidi R, Chandra M, Nelson OL et al. Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling. Journal of Physiology. 2009 Oct;587(20):4873-4886. https://doi.org/10.1113/jphysiol.2009.172544
Rodgers, Buel D. ; Interlichia, Jillian P. ; Garikipati, Dilip K. ; Mamidi, Ranganath ; Chandra, Murali ; Nelson, O. Lynne ; Murry, Charles E. ; Santana, Luis Fernando. / Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling. In: Journal of Physiology. 2009 ; Vol. 587, No. 20. pp. 4873-4886.
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