Hydrogen peroxide activates ion currents in rat mesangial cells

Hydrogen peroxide activates ion currents in rat mesangial cells. Background Hydrogen peroxide (H 2 O 2 ) is an important mediator of glomerular injury, which induces proliferation and cell contraction in mesangial cells. The aim of this study was to investigate whether and which ion currents are activated during the early cellular responses to H 2 O 2 , and to study possible mechanisms of their activation. Methods The effect of H 2 O 2 on membrane voltage of mesangial cells in short-term culture was investigated with the patch clamp technique in the fast whole cell configuration. Results H 2 O 2 contracted mesangial cells and induced a concentration-dependent biphasic membrane voltage response. One hundred μmol/liter H 2 O 2 led to a hyperpolarization of mesangial cells from -45 ± 1 to -55 ± 1 mV, which was followed by a sustained depolarization to -20 ± 3 mV. The hyperpolarization induced by H 2 O 2 was completely blocked by the K + channel blocker Ba 2+ . In the presence of a low extracellular Cl - concentration (32 mmol/liter), the depolarization induced by H 2 O 2 was significantly increased. The H 2 O 2 -induced depolarization was inhibited by 100 μmol/liter of the disulfide-reducing agent dithiothreitol, whereas higher concentrations of dithiothreitol (1 mmol/liter) were required to partially inhibit the hyperpolarization. Protein kinase C inhibitors blocked the H 2 O 2 -induced depolarization, but not the hyperpolarization. Conclusions The data indicate that H 2 O 2 leads to a biphasic membrane voltage response in mesangial cells: an initial transient hyperpolarization, which is due to the activation of a K + conductance, and a subsequent depolarization, which is, at least in part, due to the activation of a Cl - conductance. The oxidation of thiol groups by H 2 O 2 is involved in the membrane voltage response, and the depolarization may be regulated by protein kinase C.