Iron is a biologically essential metal, but excess iron can cause damage to the cardiovascular and nervous systems. We examined the effects of extracellular Fe 2ϩ on permeation and gating of Ca V 3.1 channels stably transfected in HEK293 cells, by using whole-cell recording. Precautions were taken to maintain iron in the Fe 2ϩ state (e.g., use of extracellular ascorbate). With the use of instantaneous I-V currents (measured after strong depolarization) to isolate the effects on permeation, extracellular Fe 2ϩ rapidly blocked currents with 2 mM extracellular Ca 2ϩ in a voltage-dependent manner, as described by a Woodhull model with K D ϭ 2.5 mM at 0 mV and apparent electrical distance ␦ ϭ 0.17. Extracellular Fe 2ϩ also shifted activation to more-depolarized voltages (by ϳ10 mV with 1.

Cd2ϩ is an industrial pollutant that can cause cytotoxicity in multiple organs. We examined the effects of extracellular Cd 2ϩ on permeation and gating of Ca v 3.1 (␣1G) 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, Cd 2ϩ rapidly blocked currents with 2 mM Ca 2ϩ in a voltagedependent manner. The block caused by Cd 2ϩ was relieved at more-hyperpolarized potentials, which suggests that Cd 2ϩ can permeate through the selectivity filter of the channel into the cytosol. In the absence of other permeant ions (Ca 2ϩ and Na