PT  - JOURNAL ARTICLE
AU  - Kyle V. Lopin
AU  - Frank Thévenod
AU  - Jessica C. Page
AU  - Stephen W. Jones
TI  - Cd<sup>2+</sup> Block and Permeation of Ca<sub>V</sub>3.1 (α1G) T-Type Calcium Channels: Candidate Mechanism for Cd<sup>2+</sup> Influx
AID  - 10.1124/mol.112.080176
DP  - 2012 Dec 01
TA  - Molecular Pharmacology
PG  - 1183--1193
VI  - 82
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/82/6/1183.short
4100  - http://molpharm.aspetjournals.org/content/82/6/1183.full
SO  - Mol Pharmacol2012 Dec 01; 82
AB  - Cd2+ is an industrial pollutant that can cause cytotoxicity in multiple organs. We examined the effects of extracellular Cd2+ on permeation and gating of Cav3.1 (α1G) channels stably transfected in HEK293 cells, by using whole-cell recording. With the use of instantaneous I-V currents (measured after strong depolarization) to isolate the effects on permeation, Cd2+ rapidly blocked currents with 2 mM Ca2+ in a voltage-dependent manner. The block caused by Cd2+ was relieved at more-hyperpolarized potentials, which suggests 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 that voltage (open probability, ∼1%), which makes them a candidate pathway for Cd2+ entry into cells during Cd2+ exposure. Incubation with radiolabeled 109Cd2+ confirmed uptake of Cd2+ into cells with Cav3.1 channels.