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Hydrogen peroxide activates ion currents in rat mesangial cells
J Gloy1, K G Fischer, T N Meyer
1Department of Medicine, Albert-Ludwigs-University, Freiburg, Germany.
Kidney International
|July 20, 1999
Summary
Hydrogen peroxide (H2O2) causes mesangial cells to hyperpolarize then depolarize, involving potassium and chloride ion channels. This biphasic response is linked to thiol oxidation and protein kinase C signaling.
Area of Science:
- Cellular physiology
- Molecular mechanisms of cell signaling
Background:
- Hydrogen peroxide (H2O2) is implicated in glomerular injury.
- H2O2 induces mesangial cell proliferation and contraction.
Purpose of the Study:
- Investigate ion currents activated by H2O2 in mesangial cells.
- Elucidate the mechanisms underlying H2O2-induced cellular responses.
Main Methods:
- Patch clamp technique in fast whole-cell configuration.
- Measurement of mesangial cell membrane voltage changes.
- Pharmacological manipulation using ion channel blockers and reducing agents.
Main Results:
- H2O2 induced a biphasic membrane voltage response: initial hyperpolarization followed by depolarization.
- Hyperpolarization was blocked by Ba2+ (K+ channel blocker).
- Depolarization was enhanced in low extracellular Cl-, inhibited by dithiothreitol, and blocked by Protein Kinase C inhibitors.
Conclusions:
- H2O2 activates K+ and Cl- conductances in mesangial cells, causing biphasic voltage changes.
- Oxidation of thiol groups by H2O2 is involved in the response.
- Protein kinase C may regulate the H2O2-induced depolarization.