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

摘要

The effects of cadmium (Cd2+) 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 Cd2+ inhibited the amplitudes of I _A and I _K 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 I _A to more positive potentials. In contrast, Cd2+ caused a relatively less but still significant positive shift in the activation of I _K without effect on the inactivation curve. Cd2+ 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 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.