Channelpedia

PubMed 12805476


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.2 , Cav2.3



Title: Comparative effects of methylmercury and Hg(2+) on human neuronal N- and R-type high-voltage activated calcium channels transiently expressed in human embryonic kidney 293 cells.

Authors: Ravindra K Hajela, Shuang-Qing Peng, William D Atchison

Journal, date & volume: J. Pharmacol. Exp. Ther., 2003 Sep , 306, 1129-36

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12805476


Abstract
Expression cDNA clones of alpha1B-1 or alpha1E-3 subunits coding for human neuronal N-(Cav2.2) or R-subtype (Cav2.3) Ca2+ channels, respectively, was combined with alpha2-bdelta and beta3-a Ca2+ channel subunits, and transfected into human embryonic kidney cells for transient expression to determine whether specific types of neuronal voltage-sensitive Ca2+ channels are affected differentially by methylmercury (MeHg) and Hg2+. For both Ca2+ channel subtypes, MeHg (0.125-5.0 microM) or Hg2+ (0.1-5 microM) caused a time- and concentration-dependent reduction of current. MeHg caused an initial, rapid component and a subsequent more gradual component of inhibition. The rapid component of block was completed between 100 and 150 s after beginning treatment. At 0.125 to 1.25 microM, MeHg caused a more gradual decline in current. Apparent IC50 values were 1.3 and 1.1 microM for MeHg, and 2.2 and 0.7 microM for Hg2+ on N- and R-types, respectively. For N-type current, effects of Hg2+ were initially greater on the peak current than on the sustained current remaining at the end of a test pulse; subsequently, Hg2+ blocked both components of current. For R-type current, Hg2+ affected peak and sustained current approximately equally. Kinetics of inactivation also seemed to be affected by Hg2+ in cells expressing N-type but not R-type current. Washing with MeHg-free solution could not reverse effects of MeHg on either type of current. The effect of Hg2+ on N- but not R-type current was partially reversed by Hg2+-free wash solution. Therefore, different types of Ca2+ channels have differential susceptibility to neurotoxic mercurials even when expressed in the same cell type.