Evaluation of a Two-Site, Three-Barrier Model for Permeation in CaV3.1 (α1G) T-Type Calcium Channels: Ca2+, Ba2+, Mg2+, and Na+

Evaluation of a Two-Site, Three-Barrier Model for Permeation in CaV3.1 (α1G) T-Type Calcium... We explored the ability of a two-site, three-barrier (2S3B) Eyring model to describe recently reported data on current flow through open CaV3.1 T-type calcium channels, varying Ca2+ and Ba2+ over a wide range (100 nm–110 mm) while recording whole-cell currents over a wide voltage range (−150 mV to +100 mV) from channels stably expressed in HEK 293 cells. Effects on permeation were isolated using instantaneous current–voltage relationships (IIV) after strong, brief depolarizations to activate channels with minimal inactivation. Most experimental results were reproduced by a 2S3B model. The model described the IIV relationships, apparent affinities for permeation and block for Ca2+ and Ba2+, and shifts in reversal potential between Ca2+ and Ba2+. The fit to block by 1 mm  $$ {\text{Mg}}^{2+}_{\text{i}} $$ was reasonable, but block by $$ {\text{Mg}}^{2+}_{\text{o}} $$ was described less well. Surprisingly, fits were comparable with strong ion–ion repulsion, with no repulsion, or with intermediate values. With weak repulsion, there was a single high-affinity site, with a low-affinity site near the cytoplasmic side of the pore. With strong repulsion, the net charge of ions in the pore was near +2 over a relatively wide range of concentration and voltage, suggesting a knockoff mechanism. With strong repulsion, Ba2+ preferred the inner site, while Ca2+ preferred the outer site, potentially explaining faster entry of Ni2+ and other pore blockers when Ba2+ is the charge carrier. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Evaluation of a Two-Site, Three-Barrier Model for Permeation in CaV3.1 (α1G) T-Type Calcium Channels: Ca2+, Ba2+, Mg2+, and Na+

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Publisher
Springer-Verlag
Copyright
Copyright © 2010 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-010-9264-3
Publisher site
See Article on Publisher Site

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