Effects of Cd 2+ on transient outward and delayed rectifier potassium currents in acutely isolated rat hippocampal CA1 neurons

The effects of cadmium (Cd 2+ ) on the transient outward potassium current ( I A ) and delayed rectifier potassium current ( I K ) were investigated in acutely dissociated rat hippocampal CA1 neurons using the whole-cell patch-clamp technique. The results showed that Cd 2+ inhibited the amplitudes of I A and I K in a reversible and concentration-dependent manner, with half-maximal inhibitive concentration (IC 50 ) values of 546 ± 59 and 749 ± 53 μM, and the inhibitory effect of Cd 2+ was voltage dependent. Cd 2+ significantly shifted the steady-state activation and inactivation curve of I A to more positive potentials. In contrast, Cd 2+ caused a relatively less but still significant positive shift in the activation of I K without effect on the inactivation curve. Cd 2+ significantly slowed the recovery from inactivation of I K but had no effect on the recovery time course of I A . The results suggest that the modulation of I A and I K was most likely mediated by the interaction of Cd 2+ with a specific site on the potassium-channel protein rather than by screening of bulk surface-negative charge. The effects of Cd 2+ on the voltage-gated potassium currents may be a possible contributing mechanism for the Cd 2+ -induced neurotoxic damage. In addition, the effects of Cd 2+ on the potassium currents at concentrations that overlap with its effects on calcium currents raise concerns about its use in pharmacological or physiological studies.