Effects of Cd2+ 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 microM, 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.
Wang
Shu
S
School of Life Science, University of Science & Technology of China, Hefei, Anhui 230027, People's Republic of China.
Xing
Tai-Ran
TR
Tang
Ming-Liang
ML
Yong
Wu
W
Li
Chen-Chen
CC
Chen
Liang
L
Wang
Hui-Li
HL
Tang
Jiu-Lai
JL
Ruan
Di-Yun
DY
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D051668:Delayed Rectifier Potassium Channels; D004785:Environmental Pollutants; D024642:Potassium Channels, Voltage-Gated; D002104:Cadmium