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Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles
14:02

Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles

Published on: November 1, 2012

[Functioning of the electromechanical connection in the course of the contracture contraction]

G A Nasledov1, I E Katina, M A Kobzeva

  • 1I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Acad. Sci., 194223, St. Petersburg, pr. M. Toreza, 44, Russia.

Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova
|May 22, 2004
PubMed

Insights

Dantrolene, a calcium release blocker, differentiates muscle contraction mechanisms. It inhibits voltage-dependent calcium release (VDCR) and calcium-induced calcium-release (CICR) pathways, revealing distinct stages of muscle activation.

Area of Science:

  • Muscle physiology
  • Pharmacology
  • Calcium signaling

Context:

  • Understanding the mechanisms of muscle contraction is crucial for diagnosing and treating neuromuscular disorders.
  • Dantrolene is a known modulator of intracellular calcium release, but its precise effects on different phases of muscle activation require further elucidation.
  • Investigating the roles of voltage-dependent calcium release (VDCR) and calcium-induced calcium-release (CICR) provides insights into excitation-contraction coupling.

Purpose:

  • To investigate the differential effects of dantrolene on various stages of muscle contraction.
  • To distinguish between voltage-dependent calcium release (VDCR) and calcium-induced calcium-release (CICR) mechanisms in muscle activation.
  • To elucidate the role of extracellular calcium in different phases of muscle contracture.

Summary:

  • Dantrolene inhibited the initial phase of potassium or acetylcholine-induced contractures, which was independent of extracellular calcium, suggesting a voltage-dependent calcium release (VDCR) mechanism.
  • The sustained plateau phase of contracture was dependent on extracellular calcium and inhibited by dantrolene, indicating a calcium-induced calcium-release (CICR) mechanism involving ryanodine receptors.
  • A final low-amplitude contraction phase was unaffected by dantrolene or calcium-free conditions, implying it does not rely on ryanodine receptor-mediated calcium release.

Impact:

  • This study differentiates between VDCR and CICR pathways in muscle contraction, offering a more nuanced understanding of excitation-contraction coupling.
  • The findings have implications for the development of targeted therapies for muscle disorders by identifying specific calcium release pathways.
  • Dantrolene's differential effects highlight its potential as a pharmacological tool to probe distinct calcium signaling mechanisms in muscle tissue.

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