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 F Santana

doi:10.1113/jphysiol.2009.172544

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

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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 and Luis F Santana

The Journal of physiology, Vol.587(Pt 20), pp.4873-4886

10/15/2009

DOI: https://doi.org/10.1113/jphysiol.2009.172544

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https://hdl.handle.net/2376/105692

PMCID: PMC2770153

PMID: 19736304

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Abstract

Myocardial Contraction

Cell Line

Cell Proliferation

Myocytes, Cardiac - cytology

Calcium - metabolism

Heart Diseases - physiopathology

Heart - physiology

Humans

Adrenergic beta-Agonists - pharmacology

Cardiomegaly - physiopathology

Rats

Regeneration

Animals

Myocytes, Cardiac - drug effects

Isoproterenol - pharmacology

Heart - drug effects

Myocytes, Cardiac - metabolism

Myostatin - therapeutic use

Cell Differentiation

Heart Diseases - drug therapy

Mice

Myostatin - metabolism

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 beta-adrenergic stimulation in vivo. This was due to myostatin null ventricular myocytes having larger [Ca(2+)](i) transients and contractions and responding more strongly to beta-adrenergic stimulation than wild-type cells. Enhanced cardiac output and beta-adrenergic responsiveness of myostatin null mice was therefore due to increased SR Ca(2+) 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.

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Title: Myostatin represses physiological hypertrophy of the heart and excitation-contraction coupling
Creators: Buel D Rodgers - Department of Animal Sciences and School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA. danrodgers@wsu.edu
Jillian P Interlichia
Dilip K Garikipati
Ranganath Mamidi
Murali Chandra
O Lynne Nelson
Charles E Murry
Luis F Santana
Publication Details: The Journal of physiology, Vol.587(Pt 20), pp.4873-4886
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: England
Grant note: R01 HL085686 / NHLBI NIH HHS R03 AR051917 / NIAMS NIH HHS P01 HL003174 / NHLBI NIH HHS DK076126 / NIDDK NIH HHS HL64387 / NHLBI NIH HHS HL085686 / NHLBI NIH HHS R01 HL084642 / NHLBI NIH HHS HL084642 / NHLBI NIH HHS R24 HL064387 / NHLBI NIH HHS R01 HL064387 / NHLBI NIH HHS HL03174 / NHLBI NIH HHS U24 DK076126 / NIDDK NIH HHS AR051917 / NIAMS NIH HHS R01 HL075643 / NHLBI NIH HHS HL075643 / NHLBI NIH HHS
Identifiers: 99900546703401842
Language: English
Resource Type: Journal article