Probing Ion Binding in the Selectivity Filter of the KcsA Potassium Channel

2019 ◽  
Vol 141 (18) ◽  
pp. 7391-7398 ◽  
Author(s):  
Cédric Eichmann ◽  
Lukas Frey ◽  
Innokentiy Maslennikov ◽  
Roland Riek
Keyword(s):  
Potassium Channel ◽  
Selectivity Filter ◽  
Ion Binding ◽  
Kcsa Potassium Channel

scholarly journals Functional Consequences of a Decreased Potassium Affinity in a Potassium Channel Pore

1999 ◽  
Vol 113 (2) ◽  
pp. 347-358 ◽  
Author(s):  
Eva M. Ogielska ◽  
Richard W. Aldrich
Keyword(s):  
Potassium Channel ◽  
Binding Site ◽  
Conformational Change ◽  
Electrostatic Interactions ◽  
Selectivity Filter ◽  
Inactivation Rate ◽  
Ion Binding ◽  
Present Evidence ◽  
Channel Pore ◽  
Functional Consequences

Ions bound near the external mouth of the potassium channel pore impede the C-type inactivation conformational change (Lopez-Barneo, J., T. Hoshi, S. Heinemann, and R. Aldrich. 1993. Receptors Channels. 1:61– 71; Baukrowitz, T., and G. Yellen. 1995. Neuron. 15:951–960). In this study, we present evidence that the occupancy of the C-type inactivation modulatory site by permeant ions is not solely dependent on its intrinsic affinity, but is also a function of the relative affinities of the neighboring sites in the potassium channel pore. The A463C mutation in the S6 region of Shaker decreases the affinity of an internal ion binding site in the pore (Ogielska, E.M., and R.W. Aldrich, 1998). However, we have found that this mutation also decreases the C-type inactivation rate of the channel. Our studies indicate that the C-type inactivation effects observed with substitutions at position A463 most likely result from changes in the pore occupancy of the channel, rather than a change in the C-type inactivation conformational change. We have found that a decrease in the potassium affinity of the internal ion binding site in the pore results in lowered (electrostatic) interactions among ions in the pore and as a result prolongs the time an ion remains bound at the external C-type inactivation site. We also present evidence that the C-type inactivation constriction is quite local and does not involve a general collapse of the selectivity filter. Our data indicate that in A463C potassium can bind within the selectivity filter without interfering with the process of C-type inactivation.

scholarly journals Conductance selectivity of Na+ across the K+ channel via Na+ trapped in a tortuous trajectory

2021 ◽  
Vol 118 (12) ◽  
pp. e2017168118
Author(s):  
Kenichiro Mita ◽  
Takashi Sumikama ◽  
Masayuki Iwamoto ◽  
Yuka Matsuki ◽  
Kenji Shigemi ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Single Channel ◽  
Ion Selectivity ◽  
Carbonyl Oxygen ◽  
Selectivity Filter ◽  
K Channel ◽  
Selectivity Ratio ◽  
Channel Current ◽  
Dynamics Simulations ◽  
Kcsa Potassium Channel

Ion selectivity of the potassium channel is crucial for regulating electrical activity in living cells; however, the mechanism underlying the potassium channel selectivity that favors large K+ over small Na+ remains unclear. Generally, Na+ is not completely excluded from permeation through potassium channels. Herein, the distinct nature of Na+ conduction through the prototypical KcsA potassium channel was examined. Single-channel current recordings revealed that, at a high Na+ concentration (200 mM), the channel was blocked by Na+, and this blocking was relieved at high membrane potentials, suggesting the passage of Na+ across the channel. At a 2,000 mM Na+ concentration, single-channel Na+ conductance was measured as one-eightieth of the K+ conductance, indicating that the selectivity filter allows substantial conduit of Na+. Molecular dynamics simulations revealed unprecedented atomic trajectories of Na+ permeation. In the selectivity filter having a series of carbonyl oxygen rings, a smaller Na+ was distributed off-center in eight carbonyl oxygen-coordinated sites as well as on-center in four carbonyl oxygen-coordinated sites. This amphipathic nature of Na+ coordination yielded a continuous but tortuous path along the filter. Trapping of Na+ in many deep free energy wells in the filter caused slow elution. Conversely, K+ is conducted via a straight path, and as the number of occupied K+ ions increased to three, the concerted conduction was accelerated dramatically, generating the conductance selectivity ratio of up to 80. The selectivity filter allows accommodation of different ion species, but the ion coordination and interactions between ions render contrast conduction rates, constituting the potassium channel conductance selectivity.

scholarly journals Accessibility of Cations to the Selectivity Filter of KcsA in the Inactivated State: An Equilibrium Binding Study

2019 ◽  
Vol 20 (3) ◽  
pp. 689 ◽  
Author(s):  
Ana Giudici ◽  
Maria Renart ◽  
Clara Díaz-García ◽  
Andrés Morales ◽  
José Poveda ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Binding Sites ◽  
Cation Binding ◽  
Selectivity Filter ◽  
Ion Binding ◽  
Channel State ◽  
Equilibrium Conditions ◽  
Equilibrium Binding ◽  
Potassium Channel Kcsa ◽  
Ion Binding Sites

Cation binding under equilibrium conditions has been used as a tool to explore the accessibility of permeant and nonpermeant cations to the selectivity filter in three different inactivated models of the potassium channel KcsA. The results show that the stack of ion binding sites (S1 to S4) in the inactivated filter models remain accessible to cations as they are in the resting channel state. The inactivated state of the selectivity filter is therefore “resting-like” under such equilibrium conditions. Nonetheless, quantitative differences in the apparent KD’s of the binding processes reveal that the affinity for the binding of permeant cations to the inactivated channel models, mainly K+, decreases considerably with respect to the resting channel. This is likely to cause a loss of K+ from the inactivated filter and consequently, to promote nonconductive conformations. The most affected site by the affinity loss seems to be S4, which is interesting because S4 is the first site to accommodate K+ coming from the channel vestibule when K+ exits the cell. Moreover, binding of the nonpermeant species, Na+, is not substantially affected by inactivation, meaning that the inactivated channels are also less selective for permeant versus nonpermeant cations under equilibrium conditions.

Ion Binding Affinity in the Cavity of the KcsA Potassium Channel†

Biochemistry ◽  
2004 ◽  
Vol 43 (17) ◽  
pp. 4978-4982 ◽  
Author(s):  
Yufeng Zhou ◽  
Roderick MacKinnon
Keyword(s):  
Potassium Channel ◽  
Binding Affinity ◽  
Ion Binding ◽  
Kcsa Potassium Channel
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