Rotenone inhibits delayed rectifier K+ current via a protein kinase A-dependent mechanism

Voltage-gated K+ channels (K(V)) regulate cell electrical properties, proliferation, migration, and death. Rotenone is a mitochondrial inhibitor, influencing activity of many channels that potentially participate in cell death processes, but its effect on K(V) channel in neurons remains unclear. This study used whole-cell patch clamp methods and found that rotenone concentration dependently decreased delayed rectifier K+ current (I(DR)) amplitude in cultured ventral mesencephalic neurons, but had no effect on A-type current (I(A)) peak amplitude. Furthermore, the protein kinase A inhibitor H-89 prevented rotenone-induced decrease in I(DR). The inhibition of I(DR) by rotenone was mimicked by extracellular application of forskolin. In summary, our results indicate that rotenone acutely decreased I(DR) currents in cultured mesencephalic neurons via a protein kinase A-dependent mechanism.