title: Inhibition of delayed rectifier K+ currents by copper in acutely dissociated rat hippocampal CA1 neurons.
abstract: A growing number of research results demonstrate that copper is an important trace element to life. In this study, whole-cell recording made from acutely dissociated rat hippocampal CA1 neurons was employed to investigate the actions of copper (Cu(2+)) on the delayed rectifier K(+) currents (I(K)). External application of various concentrations of Cu(2+) (1-1000microM) reduced the amplitude of I(K) in a dose-dependent manner with an IC(50) value of 100microM and a Hill coefficient of 0.4. 300microM of Cu(2+) depolarized the I(K) activation curves by 12.5mV and hyperpolarized the I(K) state-inactivation curves by 17.4mV, respectively. At this concentration, Cu(2+) also significantly increased the value of the fast decay time constant (tau(1)), but had no effect on the I(K) recovery from inactivation. These results suggest that relevant concentrations of copper at physiological and pathological level can influence the neuronal excitability of rat hippocampal CA1 neurons by voltage-gated delayed rectifier K(+) channels, and such actions are likely involved in the pathophysiology of Cu-related Wilson's disease.
authors.affiliation: School of Life Science, University of Science and Technology of China, Jinzhai Road 86, Hefei 230027, PR China.
authors.forename: Zhi-Dian
authors.initials: ZD
authors.lastname: Niu
authors.forename: Ju-Tao
authors.initials: JT
authors.lastname: Chen
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Li
authors.forename: Di-Yun
authors.initials: DY
authors.lastname: Ruan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats
chemical_list: D051668:Delayed Rectifier Potassium Channels; D003300:Copper