Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating

Kim, Dorothy M.; Nimigean, Crina M.

doi:10.1101/cshperspect.a029231

Cited by 119 publications

(89 citation statements)

References 154 publications

(194 reference statements)

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“…KcsA is a K + channel from the bacterium Streptomyces lividans with no explicit VSD 94,95 . Given its similarities to eukaryotic inwardly rectifying K + channels and the pore domain of K V channels, the structure and activity of KcsA has been intensely studied in the past 2 decades as a model protein for permeation and C-type or “slow” inactivation in ion channels 96 . The activity of KcsA is controlled by hydrogen ions; fast decrease of the pH in the intracellular side activates the channels.…”

Section: Introductionmentioning

confidence: 99%

Hysteresis in voltage-gated channels

Villalba-Galea

2016

Channels

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Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels.

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Section: Introductionmentioning

confidence: 99%

Hysteresis in voltage-gated channels

Villalba-Galea

2016

Channels

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“…7). Therefore, these results suggest that changes of the membrane potential are sensed by the S4 translocation that are 12 Å at the largest, leading to the allosteric regulation of the gating at the PD229.…”

Section: Discussionmentioning

confidence: 81%

Disulfide mapping the voltage-sensing mechanism of a voltage-dependent potassium channel

Nozaki

Ozawa

Harada

et al. 2016

Sci Rep

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Voltage-dependent potassium (Kv) channels allow for the selective permeability of potassium ions in a membrane potential dependent manner, playing crucial roles in neurotransmission and muscle contraction. Kv channel is a tetramer, in which each subunit possesses a voltage-sensing domain (VSD) and a pore domain (PD). Although several lines of evidence indicated that membrane depolarization is sensed as the movement of helix S4 of the VSD, the detailed voltage-sensing mechanism remained elusive, due to the difficulty of structural analyses at resting potential. In this study, we conducted a comprehensive disulfide locking analysis of the VSD using 36 double Cys mutants, in order to identify the proximal residue pairs of the VSD in the presence or absence of a membrane potential. An intramolecular SS-bond was formed between 6 Cys pairs under both polarized and depolarized environment, and one pair only under depolarized environment. The multiple conformations captured by the SS-bond can be divided by two states, up and down, where S4 lies on the extracellular and intracellular sides of the membrane, respectively, with axial rotation of 180°. The transition between these two states is caused by the S4 translocation of 12 Å, enabling allosteric regulation of the gating at the PD.

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“…A combination of molecular dynamics simulations and electrophysiology suggested that conformational changes at the cytosolic end of the pore act to remove steric restraints at the selectivity filter, producing structural fluctuations. These may reduce K + affinity and increase ion permeation, leading to a conducting (open) state; after opening, however, these movements may be coupled to further structural changes at the selectivity filter that block permeation, leading to an inactivated state (Figure 2B) [185–188]. These observations are consistent with combined electrophysiological and computational studies in MthK, which show that reduction in extracellular K + can lead to K + dissociation, followed by structural changes in the selectivity filter to a non-conducting state [108, 164].…”

Section: Key Questions Subject To Interdisciplinary Study In Ion Tmentioning

confidence: 99%

Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport

Howard¹,

Carnevale²,

Delemotte³

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data management and conceptual alignment. Here, we seek to provide contemporary context, concrete examples, and a look to the future for bridging disciplinary gaps in biological ion transport. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain.

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Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating

Cited by 119 publications

References 154 publications

Hysteresis in voltage-gated channels

Hysteresis in voltage-gated channels

Disulfide mapping the voltage-sensing mechanism of a voltage-dependent potassium channel

Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport

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