Effects of Cd2+ on transient outward and delayed rectifier potassium currents in acutely isolated rat hippocampal CA1 neurons

The effects of cadmium (Cd2+) on the transient outward potassium current (IA) and delayed rectifier potassium current (IK) were investigated in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch-clamp technique. The results showed that Cd2+ inhibited the amplitudes of IA and IK in a reversible and concentration-dependent manner, with half-maximal inhibitive concentration (IC50) values of 546 ± 59 and 749 ± 53 μM, and the inhibitory effect of Cd2+ was voltage dependent. Cd2+ significantly shifted the steady-state activation and inactivation curve of IA to more positive potentials. In contrast, Cd2+ caused a relatively less but still significant positive shift in the activation of IK without effect on the inactivation curve. Cd2+ significantly slowed the recovery from inactivation of IK but had no effect on the recovery time course of IA. The results suggest that the modulation of IA and IK was most likely mediated by the interaction of Cd2+ with a specific site on the potassium-channel protein rather than by screening of bulk surface-negative charge. The effects of Cd2+ on the voltage-gated potassium currents may be a possible contributing mechanism for the Cd2+-induced neurotoxic damage. In addition, the effects of Cd2+ on the potassium currents at concentrations that overlap with its effects on calcium currents raise concerns about its use in pharmacological or physiological studies.