Effects of copper on A-type potassium currents in acutely dissociated rat hippocampal CAI neurons

The effects of copper on voltage-gated A-type potassium currents were investigated in acutely dissociated rat hippocampal CAI neurons using the whole-cell patch-clamp technique. Extracellular application of various concentrations of copper (1-1000 mu M) reversibly reduced the amplitude of voltage-gated A-type potassium currents in a dose-dependent manner with a 50% inhibitory concentration value of 130 mu M. Copper (300 mu M) increased the V-1/2 of the activation curve and state-inactivation curve by 17.2 and 9.0 mV, respectively Thus, copper slowed down the activation and inactivation process of voltage-gated A-type potassium currents. This study indicated that copper reversibly inhibits the hippocampal CAI neuronal voltage-gated A-type potassium current in a dose-dependent and voltage-dependent manner, and such actions are likely involved in the regulation of the neuronal excitability and the pathophysiology of Wilson's disease.