p38 mitogen-activated protein kinase independent SB203580 block of H2O2-induced increase in GABAergic mIPSC amplitude.

Hydrogen peroxide may serve as a diffusible intermediary messenger under physiological and pathophysiological conditions. H2O2 (1 mM) increased the amplitude of GABAergic miniature inhibitory postsynaptic currents in substantia gelatinosa of the spinal cord. This effect of H2O2 was reversed by the p38 antagonist SB203580, but not by the extracellular signal-regulated kinase 1/2 antagonist PD98059, or the Jun N-terminal kinase antagonist, SP600125. Western blot analysis, however, demonstrated a maximally activated mitogen-activated protein kinase of the slice preparation with no further increase in the phospho-mitogen activated protein kinase by H2O2. Confocal microscopy documented no occult neuronal phospho-p38 induction not detected by Western blot. We conclude that SB203580 blocks H2O2-induced increase in GABAergic miniature inhibitory postsynaptic amplitude independent of its action on p38 mitogen activated protein kinase.