The Journal of General Physiology
Avanti Polar Lipids
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Published online Apr 24 2006. doi:10.1085/jgp.200509482
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 127, Number 5, 557-576
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ARTICLE

Relationship between Pore Occupancy and Gating in BK Potassium Channels



Rebecca A. Piskorowski and Richard W. Aldrich

Section of Neurobiology, University of Texas at Austin, Austin, TX 78712

Correspondence to Richard W. Aldrich: raldrich{at}mail.utexas.edu

Permeant ions can have significant effects on ion channel conformational changes. To further understand the relationship between ion occupancy and gating conformational changes, we have studied macroscopic and single-channel gating of BK potassium channels with different permeant monovalent cations. While the slopes of the conductance–voltage curve were reduced with respect to potassium for all permeant ions, BK channels required stronger depolarization to open only when thallium was the permeant ion. Thallium also slowed the activation and deactivation kinetics. Both the change in kinetics and the shift in the GV curve were dependent on the thallium passing through the permeation pathway, as well as on the concentration of thallium. There was a decrease in the mean open time and an increase in the number of short flicker closing events with thallium as the permeating ion. Mean closed durations were unaffected. Application of previously established allosteric gating models indicated that thallium specifically alters the opening and closing transition of the channel and does not alter the calcium activation or voltage activation pathways. Addition of a closed flicker state into the allosteric model can account for the effect of thallium on gating. Consideration of the thallium concentration dependence of the gating effects suggests that the flicker state may correspond to the collapsed selectivity filter seen in crystal structures of the KcsA potassium channel under the condition of low permeant ion concentration.


R.A. Piskorowski's present address is Department of Physiology, University of California at San Francisco, San Francisco, CA 94107.

Abbreviation used in this paper: NMG, N-methyl glucamine.


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