title: Cd²⁺ block and permeation of CaV3.1 (α1G) T-type calcium channels: candidate mechanism for Cd²⁺ influx.
abstract: Cd²⁺ is an industrial pollutant that can cause cytotoxicity in multiple organs. We examined the effects of extracellular Cd²⁺ on permeation and gating of Ca(v)3.1 (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 Ca(v)3.1 channels (210 ± 20 pA at -60 mV with 2 mM Cd²⁺). Ca(v)3.1 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 Ca(v)3.1 channels.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Kyle V
authors.initials: KV
authors.lastname: Lopin
authors.forename: Frank
authors.initials: F
authors.lastname: Thévenod
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Page
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Jones
mesh_terms: D002104:Cadmium / Q000378:metabolism* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods
chemical_list: C121855:CACNA1G protein, human; D020747:Calcium Channels, T-Type; D002104:Cadmium; D002118:Calcium