Reactive oxygen species impair Slo1 BK channel function by altering cysteine-mediated calcium sensing

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Xiang Dong Tang1, Maria L Garcia, Stefan H Heinemann

  • 1Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.

Nature Structural & Molecular Biology
|January 28, 2004
PubMed

Insights

Reactive oxygen species (ROS) inhibit vascular smooth muscle calcium-dependent potassium channels (BK channels), contributing to vascular dysfunction. Targeting these channels may offer new treatments for cardiovascular diseases.

Area of Science:

  • Cardiovascular Science
  • Molecular Biology
  • Physiology

Background:

  • Vascular dysfunction underlies diseases like coronary heart disease, stroke, and diabetes.
  • Inflammation and oxidative stress from reactive oxygen species (ROS) are implicated but mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of ROS in vascular smooth muscle dysfunction.
  • To elucidate the molecular mechanisms by which ROS affect vascular tone via potassium channels.

Main Methods:

  • Electrophysiological studies on vascular smooth muscle calcium-dependent Slo1 BK (or Maxi-K) potassium channels.
  • Investigated the effect of hydrogen peroxide (H2O2) on channel activation.
  • Examined the specific cysteine residue targeted by H2O2.

Main Results:

  • ROS, specifically H2O2, were found to be potent inhibitors of Slo1 BK channels.
  • H2O2 targets a cysteine residue near the Ca(2+) bowl of the BK alpha subunit.
  • This inhibition significantly reduces physiological channel activation, comparable to beta 1 subunit knockout.

Conclusions:

  • Reveals a molecular basis for vascular dysfunction linked to oxidative stress.
  • Suggests that ROS directly impair BK channel function, impacting vascular tone.
  • Provides a rationale for developing BK channel openers for cardiovascular disorder treatment and prevention.

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