Abstract
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.
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Acknowledgements
This work was supported by the National Basic Research Program of China (No. 2002CB512907), the National Nature Science Foundation of China (No. 30630057; 30670554; 30670662; 30672290), Academia Sinica (No. KZCX3-SW-437), China Postdoctoral Science Foundation (No. 20060400719) and K.C. Wong Education Foundation of Hong Kong.
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Wang, S., Xing, TR., Tang, ML. et al. Effects of Cd2+ on transient outward and delayed rectifier potassium currents in acutely isolated rat hippocampal CA1 neurons. Naunyn-Schmied Arch Pharmacol 377, 245–253 (2008). https://doi.org/10.1007/s00210-008-0278-7
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DOI: https://doi.org/10.1007/s00210-008-0278-7