Hydrogen peroxide activates ion currents in rat mesangial cells

Background. Hydrogen peroxide (H2O2) is an important mediator of glomerular injury, which induces proliferation and cell contraction in mesangial cell s. The aim of this study was to investigate whether and which ion currents are activated during the early cellular responses to H2O2. and to study pos sible mechanisms of their activation. Methods. The effect of H2O2 on membrane voltage of mesangial cells in short -term culture was investigated with the patch clamp technique in the fast w hole cell configuration. Results. H2O2 contracted mesangial cells and induced a concentration-depend ent biphasic membrane voltage response. One hundred mu mol/liter H2O2 led t o a hyperpolarization of mesangial cells from -45 +/- 1 to -55 +/- 1 mV, wh ich was followed by a sustained depolarization to -20 +/- 3 mV. The hyperpo larization induced by H2O2 was completely blocked by the K+ channel blocker Ba2+. In the presence of a low extracellular Cl- concentration (32 mmol/li ter), the depolarization induced by H2O2 was significantly increased. The H 2O2-induced depolarization was inhibited by 100 mu mol/liter of the disulfi de-reducing agent dithiothreitol, whereas higher concentrations of dithioth reitol (1 mmol/liter) were required to partially inhibit the hyperpolarizat ion. Protein kinase C inhibitors blocked the H2O2-induced depolarization, b ut not the hyperpolarization. Conclusions. The data indicate that H2O2 leads to a biphasic membrane volta ge response in mesangial cells: an initial transient hyperpolarization. whi ch is due to the activation of a K+ conductance, and a subsequent depolariz ation, which is, at least in part, due to the activation of a Cl- conductan ce. The oxidation of thiol groups by H2O2 is involved in the membrane volta ge response, and the depolarization may be regulated by protein kinase C.