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The mitochondrial channel VDAC has a cation-selective open state.

Evgeny Pavlov1, Sergey M Grigoriev, Laurent M Dejean

  • 1Department of Basic Sciences, New York University, College of Dentistry, 345 East 24th Street, New York, NY 10010, USA.

Biochimica Et Biophysica Acta
|November 19, 2005
PubMed
Summary

Researchers discovered a new functional state of the voltage-dependent anion channel (VDAC). This cation-selective state has high conductance, suggesting novel mechanisms for mitochondrial outer membrane permeability regulation.

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Area of Science:

  • Mitochondrial biophysics
  • Ion channel physiology

Background:

  • The mitochondrial voltage-dependent anion channel (VDAC) exhibits known open (anion-selective) and half-open (cation-selective) states.
  • Channel gating is voltage-dependent, with cation selectivity prevalent at higher membrane potentials.

Purpose of the Study:

  • To identify and characterize novel functional states of the VDAC channel.
  • To investigate the gating mechanisms and selectivity of VDAC under varying electrical conditions.

Main Methods:

  • Electrophysiological recordings of VDAC reconstituted into artificial lipid bilayers.
  • Voltage-clamp analysis to determine channel conductance and ion selectivity.

Main Results:

  • A new, high-conductance, cation-selective state of VDAC was identified.

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  • This state is accessible from both the canonical open anion-selective state and the half-open cation-selective state.
  • The transition from the open to the new cation-selective state suggests a gating mechanism independent of partial channel closure.

    • Conclusions:

    • VDAC possesses a previously unrecognized cation-selective, high-conductance functional state.
    • This finding implies a distinct selectivity gating mechanism in VDAC, separate from simple pore constriction.
    • The discovery may have significant implications for understanding mitochondrial outer membrane permeability and its physiological regulation.