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Updated: Mar 22, 2026
Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface
Matthias Eden1,2, Benjamin Meder3, Mirko Völkers3
1Department of Internal Medicine III (Cardiology and Angiology), University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Abstract:
Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca(2+) amplitudes and a lower diastolic Ca(2+) content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca(2+) transients and enhances L-type Ca(2+) channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Ca(2+)currents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease.
Insights
A novel cardiac protein, Myoscape, directly interacts with L-type calcium channels. Myoscape is crucial for maintaining heart function, and its reduction contributes to heart failure pathogenesis.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Calcium signaling is vital in heart failure pathogenesis.
- The L-type calcium channel (LTCC) is a key regulator of cardiac function.
- Understanding novel regulators of LTCC is critical for heart failure research.
Purpose of the Study:
- To identify and characterize a novel cardiac protein, Myoscape/FAM40B/STRIP2, that interacts with the L-type calcium channel.
- To elucidate the role of Myoscape in regulating calcium transients and cardiac contractility.
- To investigate the in vivo function of Myoscape in cardiac health and disease.
Main Methods:
- Investigated Myoscape's interaction with LTCC in cardiomyocytes.
- Utilized knockdown and overexpression techniques in cardiomyocytes.
- Examined cardiac function in Myoscape-depleted zebrafish and Myoscape knockout mice.
- Analyzed LTCC surface expression and calcium current densities in Myoscape-deficient models.
- Assessed Myoscape expression in human heart failure samples.
Main Results:
- Myoscape directly interacts with the L-type calcium channel.
- Myoscape knockdown in cardiomyocytes reduced calcium transients, LTCC currents, and contractility.
- Myoscape overexpression restored LTCC currents in failing cardiomyocytes.
- Myoscape-deficient zebrafish and mice exhibited impaired cardiac function and advanced heart failure.
- Myoscape deficiency led to diminished LTCC surface expression and reduced calcium current densities.
- Myoscape expression was decreased in human hearts with terminal heart failure.
Conclusions:
- Myoscape is a critical regulator of L-type calcium channel function and cardiac contractility.
- Downregulation of Myoscape contributes to the pathogenesis of heart failure.
- Myoscape represents a potential therapeutic target for heart failure treatment.
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