Effects of Pb2+ on the transient outward potassium current in acutely dissociated rat hippocampal neurons.
Modulation of the voltage-dependent transient outward potassium current (IA) by Pb2+ was studied in acutely dissociated rat hippocampal pyramidal cells from the CA1 region at postnatal ages 7-14 days using the conventional whole-cell patch-clamp technique. In the presence of different concentrations of external Pb2+, the initial delay and activation time of IA were concentration-dependently lengthened. In particular, the initial delay was even longer in 1 mM Pb2+, showing no signs of saturation. Pb2+ also slowed the inactivation of IA, for decay time constants in the presence of Pb2+ were increased under the same experimental protocols. The activation curves, which were reasonably fitted by a single Boltzmann function, illustrated that Pb2+ increased the voltage threshold of IA and shifted the normalized activation current-voltage curves to more depolarizing voltage commands. Moreover, Pb2+ significantly affected the steady-state inactivation of IA. The application of Pb 2+ made the curves of the steady-state inactivation of IA shift to more depolarizing voltages with little change in the slopes factors. In brief, the results demonstrated that Pb2+ is a dose- and voltage-dependent, reversible blocker of IA currents of hippocampal CA1 neurons. The observations were fitted by the revised "Kuo and Chen type model", which postulates a Pb2+-selective site near the pore of the IA channel and that modulation of the IA channel by Pb2+ is the result of the competitive influences of Pb2+ on opening and inactivating different pathways.
Yu
Kuai
K
School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, P.R., China.
Ge
Shao-Yu
SY
Dai
Xiao-Qing
XQ
Ruan
Di-Yun
DY
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D007854:Lead / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D015221:Potassium Channels; D007854:Lead