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.