Permeation Selectivity by Competition in a Delayed Rectifier Potassium Channel

Korn, Stephen J.; Ikeda, Stephen R.

doi:10.1126/science.7618108

Cited by 97 publications

(114 citation statements)

References 17 publications

(14 reference statements)

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“…The channel is functionally closed when the filter is in a high-affinity state because K ions are trapped. High-affinity binding sites for Ca and K ions have been experimentally demonstrated for voltage-gated Ca and K channels, respectively (23)(24)(25)(26). In inwardly rectifying K channels, short-lived closed states result from K ions getting trapped inside the pore (27), indicating the existence of a K-binding site that it is capable of gating the channel.…”

Section: Discussionmentioning

confidence: 99%

K channel gating by an affinity-switching selectivity filter

VanDongen

2004

Proc. Natl. Acad. Sci. U.S.A.

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A universal property of ion channels is their ability to alternate stochastically between two permeation states, open and closed. This behavior is thought to be controlled by a steric ''gate'', a structure that physically impedes ion flow in the closed state and moves out of the way during channel opening. Experiments employing macroscopic currents in the Shaker K channel have suggested a cytoplasmic localization for the gate. Crystallographic structures of the KcsA K channel indeed reveal a cytoplasmic constriction, implying that the gate and selectivity filter are localized to opposite ends of the permeation pathway. However, analysis of K channel subconductance behavior has suggested a strict coupling between channel opening (gating) and permeation. The idea that the selectivity filter is the gate was therefore investigated by using Monte Carlo simulations. Gating is accomplished by allowing the filter to alternate stochastically between two conformations: a high-affinity state, which selectively binds K ions (but not Na ions) and traps them, and a completely nonselective, low-affinity state, which allows both Na and K ions to permeate. The results of these simulations indicate that affinity switching not only endows the selectivity filter with gating abilities, it also allows efficient permeation without jeopardizing ion selectivity. In this model, permeation and gating result from the same process.

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Section: Discussionmentioning

confidence: 99%

K channel gating by an affinity-switching selectivity filter

VanDongen

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Enlarging the pore further, one might expect the channel to eventually become permeable to Cs + and, perhaps, hydrated Na + ions. It is interesting that Kv2.1 K + channels are surprisingly permeable to Na + in the complete absence of external and internal K + in contrast to the closely related Kv1.5 K + channels which show negligible Na + conductance after removal of K + [22]. The molecular alterations that cause this dramatic change in ion selectivity are not known; however, the fact that block by external TEA is abolished when the channel is permeable to Na + ions suggests that substantial conformational rearrangements have taken place near the outer TEAbinding site and, perhaps, have been propagated to the ion-selectivity filter.…”

Section: The Substitutions For Cys 393 Do Not Alter Block By Teamentioning

confidence: 97%

A side chain in S6 influences both open-state stability and ion permeation in a voltage-gated K + channel

Liu

Joho

1998

Pfl�gers Archiv European Journal of Physiology

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Conservative substitutions of the conserved cysteine 393 (Cys393) in S6 of the voltage-gated K+ channel Kv2.1 predictably alter the stability of the open state and the conductances for K+ and Rb+. The polarity of the side chain at position 393 determines the stability of the open state, probably by interaction of S6 with the narrow part of the ion-conduction pathway; however, the substitutions at position 393 have no effect on the stability of the closed state. An increase in side-chain volume leads to greater K+ conductance; in contrast, gradual decreases in side-chain volume lead to progressively smaller K+ conductances concomitantly with larger Rb+ conductances. Although the substitutions for Cys393 alter open-state stability and ion permeation, they have no effect on block by external or internal tetraethylammonium (TEA). Our data indicate that molecular determinants that are involved in conformational transitions between the open state and the brief closed state (i.e., voltage-independent gating) and ion selectivity are located within the sphere of influence of the conserved Cys393 in S6. This region is physically separated from the voltage-controlled activation gate located on the intracellular side of the K+ channel.

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“…This phenomenon allows the sites to equilibrate to their ion preference. In K þ channels, K þ ions would then primarily occupy the available sites in the filter, which leads to selective ion conduction under a variety of conditions 5,6,38,39,[43][44][45][46] . We propose that the reduction in the number of K þ ions bound in the two-and three-site channels effectively destroys the multi-ion selectivity mechanism utilized by K þ channels.…”

Section: Discussionmentioning

confidence: 99%

“…A variety of experimental techniques all support the conclusion that different K þ channels have a preference for K þ ions over Na þ ions at equilibrium [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] . The simplest mechanism to explain ion selectivity is that the equilibrium preference of a channel determines its selectivity during ion conduction.…”

mentioning

confidence: 90%

Equilibrium selectivity alone does not create K+-selective ion conduction in K+ channels

Liu

Lockless

2013

Nat Commun

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Potassium (K þ ) channels are selective for K þ over Na þ ions during their transport across membranes. We and others have previously shown that tetrameric K þ channels are primarily occupied by K þ ions in their selectivity filters under physiological conditions, demonstrating the channel's intrinsic equilibrium preference for K þ ions. Based on this observation, we hypothesize that the preference for K þ ions over Na þ ions in the filter determines its selectivity during ion conduction. Here, we ask whether non-selective cation channels, which share an overall structure and similar individual ion-binding sites with K þ channels, have an ion preference at equilibrium. The variants of the non-selective Bacillus cereus NaK cation channel we examine are all selective for K þ over Na þ ions at equilibrium. Thus, the detailed architecture of the K þ channel selectivity filter, and not only its equilibrium ion preference, is fundamental to the generation of selectivity during ion conduction.

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Permeation Selectivity by Competition in a Delayed Rectifier Potassium Channel

Cited by 97 publications

References 17 publications

K channel gating by an affinity-switching selectivity filter

K channel gating by an affinity-switching selectivity filter

A side chain in S6 influences both open-state stability and ion permeation in a voltage-gated K + channel

Equilibrium selectivity alone does not create K+-selective ion conduction in K+ channels

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