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Intracellular Ca(2+) release as irreversible Markov process.

Juliana Rengifo1, Rafael Rosales, Adom González

  • 1Department of Molecular Biophysics and Physiology, Rush University, 1750 W. Harrison Street, Chicago, IL 60612, USA.

Biophysical Journal
|November 5, 2002
PubMed
Summary
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Skeletal muscle fibers exhibit intrinsic calcium (Ca2+) release oscillations independent of voltage sensors. This phenomenon, driven by sarcoplasmic reticulum calcium gradients, reveals a novel energy source for muscle contraction.

Area of Science:

  • Muscle Physiology
  • Cellular Biophysics
  • Ion Channel Gating

Background:

  • Intracellular calcium (Ca2+) release in striated muscles is typically controlled by membrane voltage sensors.
  • The precise role of Ca2+ in skeletal muscle control, unlike cardiac muscle, remains incompletely understood.
  • Previous research highlights the importance of Ca2+ in cardiac muscle but leaves skeletal muscle mechanisms unclear.

Purpose of the Study:

  • To investigate intrinsic gating oscillations of Ca2+ release in skeletal muscle fibers.
  • To elucidate the underlying mechanisms and energy sources driving these oscillations.
  • To determine the location of critical Ca2+ sensing sites within the muscle fiber.

Main Methods:

  • Voltage clamp experiments on frog skeletal muscle fibers.

Related Experiment Videos

  • Development and application of a Markov model to simulate Ca2+ release unit behavior.
  • Experimental manipulation using EGTA and sarcoplasmic reticulum (SR) Ca2+ depletion.

    • Main Results:

    • Demonstrated intrinsic gating oscillations of Ca2+ release in skeletal muscle, independent of voltage sensors.
    • A Markov model successfully reproduced these oscillations, indicating a violation of thermodynamic reversibility.
    • Identified the SR [Ca2+] gradient as the energy source, with sensing sites >35 nm from the channel.

    Conclusions:

    • Skeletal muscle exhibits intrinsic, non-voltage-dependent Ca2+ release oscillations.
    • These oscillations are thermodynamically irreversible, powered by the SR Ca2+ gradient.
    • The findings reveal a novel mechanism of cell-wide oscillation driven by ion permeation and channel gating coupling.