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 Probing the Cavity of the Slow Inactivated Conformation of Shaker Potassium Channels

2007 ◽  
Vol 129 (5) ◽  
pp. 403-418 ◽  
Author(s):  
Gyorgy Panyi ◽  
Carol Deutsch
Keyword(s):  
Potassium Channels ◽  
Binding Site ◽  
Conformational Change ◽  
Marked Decrease ◽  
Selectivity Filter ◽  
Slow Inactivation ◽  
Voltage Gated ◽  
Activation Gate ◽  
Shaker Potassium Channels

Slow inactivation involves a local rearrangement of the outer mouth of voltage-gated potassium channels, but nothing is known regarding rearrangements in the cavity between the activation gate and the selectivity filter. We now report that the cavity undergoes a conformational change in the slow-inactivated state. This change is manifest as altered accessibility of residues facing the aqueous cavity and as a marked decrease in the affinity of tetraethylammonium for its internal binding site. These findings have implications for global alterations of the channel during slow inactivation and putative coupling between activation and slow-inactivation gates.

scholarly journals Structural and Functional Consequences of an Amide-to-Ester Substitution in the Selectivity Filter of a Potassium Channel

2006 ◽  
Vol 128 (35) ◽  
pp. 11591-11599 ◽  
Author(s):  
Francis I. Valiyaveetil ◽  
Matthew Sekedat ◽  
Roderick MacKinnon ◽  
Tom W. Muir
Keyword(s):  
Potassium Channel ◽  
Selectivity Filter ◽  
Functional Consequences

scholarly journals Structure of human sodium leak channel NALCN in complex with FAM155A

2020 ◽  
Author(s):  
Jiongfang Xie ◽  
Meng Ke ◽  
Lizhen Xu ◽  
Shiyi Lin ◽  
Jin Huang ◽  
...  
Keyword(s):  
Binding Site ◽  
Molecular Basis ◽  
Neuronal Excitability ◽  
Selectivity Filter ◽  
Ion Binding ◽  
Voltage Sensitivity ◽  
Auxiliary Subunits ◽  
Leak Channel ◽  
Extracellular Loops ◽  
Central Nervous Systems

Abstract NALCN, a sodium leak channel mainly expressed in the central nervous systems, is responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases. Here, we reported the cryo-EM structure of human NALCN in complex with FAM155A, at an overall resolution of 3.1 angstrom. FAM155A forms extensive interactions with the extracellular loops of NALCN that help stabilize NALCN in the membrane. A Na+ ion-binding site, reminiscent of a Ca2+ binding site in Cav channels, is identified in the unique EEKE selectivity filter. Despite its ‘leaky’ nature, the intracellular gate is sealed by S6I, II-III linker and III-IV linker. Our study establishes the molecular basis of Na+ permeation and voltage sensitivity, and provides important clues to the mechanistic understanding of NALCN regulation and NALCN channelosome-related diseases.

scholarly journals Calmodulin acts as a state-dependent switch to control a cardiac potassium channel opening

2020 ◽  
Author(s):  
Po Wei Kang ◽  
Annie M. Westerlund ◽  
Jingyi Shi ◽  
Kelli McFarland White ◽  
Alex K. Dou ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Conformational Change ◽  
State Dependent ◽  
Gating Mechanism ◽  
Channel Opening ◽  
Activated State ◽  
Voltage Dependent ◽  
Functional Consequences ◽  
Pore Opening ◽  
Voltage Sensing Domain

AbstractCalmodulin (CaM) and PIP2 are potent regulators of the voltage-gated potassium channel KCNQ1 (KV7.1), which conducts the IKs current important for repolarization of cardiac action potentials. Although cryo-EM structures revealed intricate interactions between the KCNQ1 voltage-sensing domain (VSD), CaM, and PIP2, the functional consequences of these interactions remain unknown. Here, we show that CaM-VSD interactions act as a state-dependent switch to control KCNQ1 pore opening. Combined electrophysiology and molecular dynamics network analysis suggest that VSD transition into the fully-activated state allows PIP2 to compete with CaM for binding to VSD, leading to the conformational change that alters the VSD-pore coupling. We identify a motif in the KCNQ1 cytosolic domain which works downstream of CaM-VSD interactions to facilitate the conformational change. Our findings suggest a gating mechanism that integrates PIP2 and CaM in KCNQ1 voltage-dependent activation, yielding insights into how KCNQ1 gains the phenotypes critical for its function in the heart.

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 Structural basis for C-type inactivation in a Shaker family voltage gated K+ channel

2021 ◽  
Author(s):  
Ravikumar Reddi ◽  
Kimberly Matulef ◽  
Erika A. Riederer ◽  
Matthew R. Whorton ◽  
Francis I. Valiyaveetil
Keyword(s):  
Crystal Structure ◽  
Binding Sites ◽  
Structural Changes ◽  
Selectivity Filter ◽  
Structural Basis ◽  
K Channel ◽  
Ion Binding ◽  
Channel Pore ◽  
Voltage Gated ◽  
Ion Binding Sites

AbstractC-type inactivation is a process by which ion flux through a voltage-gated K+ (Kv) channel is regulated at the selectivity filter. While prior studies have indicated that C-type inactivation involves structural changes at the selectivity filter, the nature of the changes have not been resolved. Here we report the crystal structure of the Kv1.2 channel in a C-type inactivated state. The structure shows that C-type inactivation involves changes in the selectivity filter that disrupt the outer two ion binding sites in the filter. The changes at the selectivity filter propagate to the extracellular mouth and the turret regions of the channel pore. The structural changes observed are consistent with the functional hallmarks of C-type inactivation. This study highlights the intricate interplay between K+ occupancy at the ion binding sites and the interactions of the selectivity filter in determining the balance between the conductive and the inactivated conformations of the filter.

scholarly journals Polyamine block of MthK potassium channels

2020 ◽  
Vol 152 (7) ◽  
Author(s):  
Crina M. Nimigean
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Binding Site ◽  
Ion Flux ◽  
Membrane Excitability ◽  
Channel Pore

Polyamines can modulate membrane excitability by blocking ion flux through ion channels. Suma et al. determined the location of the binding site for polyamines inside a model potassium channel pore.

scholarly journals Transmembrane allosteric energetics characterization for strong coupling between proton and potassium ion binding in the KcsA channel

2017 ◽  
Vol 114 (33) ◽  
pp. 8788-8793 ◽  
Author(s):  
Yunyao Xu ◽  
Manasi P. Bhate ◽  
Ann E. McDermott
Keyword(s):  
Ion Channel ◽  
Binding Site ◽  
Ph Sensor ◽  
Selectivity Filter ◽  
Ion Binding ◽  
Wild Type ◽  
Channel Activation ◽  
Site Specific ◽  
Allosteric Coupling ◽  
Allosteric Mechanism

The slow spontaneous inactivation of potassium channels exhibits classic signatures of transmembrane allostery. A variety of data support a model in which the loss of K+ ions from the selectivity filter is a major factor in promoting inactivation, which defeats transmission, and is allosterically coupled to protonation of key channel activation residues, more than 30 Å from the K+ ion binding site. We show that proton binding at the intracellular pH sensor perturbs the potassium affinity at the extracellular selectivity filter by more than three orders of magnitude for the full-length wild-type KcsA, a pH-gated bacterial channel, in membrane bilayers. Studies of F103 in the hinge of the inner helix suggest an important role for its bulky sidechain in the allosteric mechanism; we show that the energetic strength of coupling of the gates is strongly altered when this residue is mutated to alanine. These results provide quantitative site-specific measurements of allostery in a bilayer environment, and highlight the power of describing ion channel gating through the lens of allosteric coupling.

scholarly journals Structure of a Prokaryotic Sodium Channel Pore Reveals Essential Gating Elements and an Outer Ion Binding Site Common to Eukaryotic Channels

2014 ◽  
Vol 106 (2) ◽  
pp. 130a
Author(s):  
Cristina Arrigoni ◽  
David Shaya ◽  
Felix Findeisen ◽  
Fayal Abdermane-Ali ◽  
Gildas Loussouarn ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Binding Site ◽  
Ion Binding ◽  
Channel Pore
Sign in / Sign up

Export Citation Format

Share Document