TY - JOUR T1 - Cd<sup>2+</sup> Block and Permeation in CaV3.1 (α1G) T-type Calcium Channels. A Candidate Mechanism for Cd<sup>2+</sup> Influx JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.080176 SP - mol.112.080176 AU - Kyle V. Lopin AU - Frank Thevenod AU - Jessica C. Page AU - Stephen W. Jones Y1 - 2012/01/01 UR - http://molpharm.aspetjournals.org/content/early/2012/09/12/mol.112.080176.abstract N2 - Cd2+ is an industrial pollutant that can cause cytotoxicity in multiple organs. We have examined the effects of Cd2+o on permeation and gating in Cav3.1 (α1G) channels, stably transfected in HEK 293 cells, using whole-cell recording. Using instantaneous I-V currents (measured following strong depolarization) to isolate effects on permeation, Cd2+ rapidly blocked currents with 2 mM Ca2+ in a voltage-dependent manner. The block caused by Cd2+ is relieved at more hyperpolarized potentials, suggesting that Cd2+ can permeate through the selectivity filter of the channel into the cytosol. In the absence of other permeant ions (Ca2+ and Na+ replaced by N-methyl D-glucamine) Cd2+ carried sizable inward currents through Cav3.1 channels (210 ± 20 pA at -60 mV with 2 mM Cd2+). Cav3.1 channels have a significant 'window current' at this voltage (Popen ~ 1%) making them a candidate pathway for Cd2+ entry into cells during Cd2+ exposure. Incubation with radiolabeled 109Cd2+o confirmed that Cav3.1 channels can lead to the uptake of Cd2+o into cells. ER -