scholarly journals Physical and Chemical Interplay Between the Membrane and a Prototypical Potassium Channel Reconstituted on a Lipid Bilayer Platform

2021 ◽  
Vol 14 ◽  
Author(s):  
Masayuki Iwamoto ◽  
Shigetoshi Oiki
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
Molecular Mechanism ◽  
Lipid Bilayer ◽  
Membrane Tension ◽  
Potassium Channel Kcsa ◽  
Membrane Effects ◽  
Physical Features ◽  
Physical And Chemical ◽  
Specific Lipid

Once membrane potential changes or ligand binding activates the ion channel, the activity of the channel is finely modulated by the fluctuating membrane environment, involving local lipid composition and membrane tension. In the age of post-structural biology, the factors in the membrane that affect the ion channel function and how they affect it are a central concern among ion channel researchers. This review presents our strategies for elucidating the molecular mechanism of membrane effects on ion channel activity. The membrane’s diverse and intricate effects consist of chemical and physical processes. These elements can be quantified separately using lipid bilayer methods, in which a membrane is reconstructed only from the components of interest. In our advanced lipid bilayer platform (contact bubble bilayer, CBB), physical features of the membrane, such as tension, are freely controlled. We have elucidated how the specific lipid or membrane tension modulates the gating of a prototypical potassium channel, KcsA, embedded in the lipid bilayer. Our results reveal the molecular mechanism of the channel for sensing and responding to the membrane environment.

scholarly journals Conformational heterogeneity in closed and open states of the KcsA potassium channel in lipid bicelles

2016 ◽  
Vol 148 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Dorothy M. Kim ◽  
Igor Dikiy ◽  
Vikrant Upadhyay ◽  
David J. Posson ◽  
David Eliezer ◽  
...  
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
Conformational Changes ◽  
Ph Dependence ◽  
Channel Gating ◽  
Conformational Heterogeneity ◽  
Ion Channel Gating ◽  
Potassium Channel Kcsa ◽  
Functional States ◽  
Open States

The process of ion channel gating—opening and closing—involves local and global structural changes in the channel in response to external stimuli. Conformational changes depend on the energetic landscape that underlies the transition between closed and open states, which plays a key role in ion channel gating. For the prokaryotic, pH-gated potassium channel KcsA, closed and open states have been extensively studied using structural and functional methods, but the dynamics within each of these functional states as well as the transition between them is not as well understood. In this study, we used solution nuclear magnetic resonance (NMR) spectroscopy to investigate the conformational transitions within specific functional states of KcsA. We incorporated KcsA channels into lipid bicelles and stabilized them into a closed state by using either phosphatidylcholine lipids, known to favor the closed channel, or mutations designed to trap the channel shut by disulfide cross-linking. A distinct state, consistent with an open channel, was uncovered by the addition of cardiolipin lipids. Using selective amino acid labeling at locations within the channel that are known to move during gating, we observed at least two different slowly interconverting conformational states for both closed and open channels. The pH dependence of these conformations and the predictable disruptions to this dependence observed in mutant channels with altered pH sensing highlight the importance of conformational heterogeneity for KcsA gating.

The potassium channel KcsA and its interaction with the lipid bilayer

2003 ◽  
Vol 60 (8) ◽  
pp. 1581-1590 ◽  
Author(s):  
I. M. Williamson ◽  
S. J. Alvis ◽  
J. M. East ◽  
A. G. Lee
Keyword(s):  
Potassium Channel ◽  
Lipid Bilayer ◽  
Potassium Channel Kcsa

scholarly journals A Lipid Bilayer Formed on a Hydrogel Bead for Single Ion Channel Recordings

Micromachines ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1070
Author(s):  
Minako Hirano ◽  
Daiki Yamamoto ◽  
Mami Asakura ◽  
Tohru Hayakawa ◽  
Shintaro Mise ◽  
...  
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
Lipid Bilayer ◽  
Drug Targets ◽  
Bk Channel ◽  
Voltage Dependent Anion Channel ◽  
Hydrogel Bead ◽  
Cell Functions ◽  
Channel Proteins ◽  
Measurement Efficiency

Ion channel proteins play important roles in various cell functions, making them attractive drug targets. Artificial lipid bilayer recording is a technique used to measure the ion transport activities of channel proteins with high sensitivity and accuracy. However, the measurement efficiency is low. In order to improve the efficiency, we developed a method that allows us to form bilayers on a hydrogel bead and record channel currents promptly. We tested our system by measuring the activities of various types of channels, including gramicidin, alamethicin, α-hemolysin, a voltage-dependent anion channel 1 (VDAC1), a voltage- and calcium-activated large conductance potassium channel (BK channel), and a potassium channel from Streptomyces lividans (KcsA channel). We confirmed the ability for enhanced measurement efficiency and measurement system miniaturizion.

scholarly journals The study of sodium and potassium channel gene single-nucleotide variation significance in non-mechanical forms of epilepsy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ozada Khamdiyeva ◽  
Zhanerke Tileules ◽  
Gulminyam Baratzhanova ◽  
Anastassiya Perfilyeva ◽  
Leyla Djansugurova
Keyword(s):  
Ion Channel ◽  
Potassium Channel ◽  
De Novo ◽  
Potassium Ion ◽  
Dravet Syndrome ◽  
De Novo Mutations ◽  
Single Nucleotide ◽  
Channel Gene ◽  
Sodium And Potassium ◽  
Potassium Channel Gene

Abstract Background Epilepsy is one of the most common and heterogeneous neurological diseases. The main clinical signs of the disease are repeated symptomatic or idiopathic epileptic seizures of both convulsive and non-convulsive nature that develop against a background of lost or preserved consciousness. The genetic component plays a large role in the etiology of idiopathic forms of epilepsy. The study of the molecular genetic basis of neurological disorders has led to a rapidly growing number of gene mutations known to be involved in hereditary ion channel dysfunction. The aim of this research was to evaluate the involvement of single-nucleotide variants that modify the function of genes (SCN1A, KCNT1, KCNTС1, and KCNQ2) encoding sodium and potassium ion channel polypeptides in the development of epilepsy. Results De novo mutations in the sodium channel gene SCN1A c.5347G>A (p. Ala1783Thr) were detected in two patients with Dravet syndrome, with a deletion in exon 26 found in one. Three de novo mutations in the potassium channel gene KCNT1 c.2800G>A (p. Ala934Thr), were observed in two patients with temporal lobe epilepsy (TLE) and one patient with residual encephalopathy. Moreover, a control cohort matched to the case cohort did not reveal any SNVs among conditionally healthy individuals, supporting the pathogenic significance of the studied SNVs. Conclusion Our results are supported by literature data showing that the sodium ion channel gene SCN1A c.5347G>A mutation may be involved in the pathogenesis of Dravet syndrome. We also note that the c.2800G>A mutation in the potassium channel gene KCNT1 can cause not only autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) but also other forms of epilepsy. To treat pathogenetic mutations that accelerate the function of sodium and potassium ion channels, we recommend ion channel blockade drug therapy.

Voltage-induced gating of the mechanosensitive MscL ion channel reconstituted in a tethered lipid bilayer membrane

2008 ◽  
Vol 23 (6) ◽  
pp. 919-923 ◽  
Author(s):  
Martin Andersson ◽  
George Okeyo ◽  
Danyell Wilson ◽  
Henk Keizer ◽  
Paul Moe ◽  
...  
Keyword(s):  
Ion Channel ◽  
Lipid Bilayer ◽  
Bilayer Membrane ◽  
Lipid Bilayer Membrane

scholarly journals Characterizing the Fatty Acid Binding Site in the Cavity of Potassium Channel KcsA

Biochemistry ◽  
2012 ◽  
Vol 51 (40) ◽  
pp. 7996-8002 ◽  
Author(s):  
Natalie Smithers ◽  
Juan H. Bolivar ◽  
Anthony G. Lee ◽  
J. Malcolm East
Keyword(s):  
Fatty Acid ◽  
Potassium Channel ◽  
Binding Site ◽  
Fatty Acid Binding ◽  
Potassium Channel Kcsa ◽  
Fatty Acid Binding Site

Automatable lipid bilayer formation for ion channel studies

2008 ◽  
Author(s):  
Jason L. Poulos ◽  
Hyunwoo Bang ◽  
Tae-Joon Jeon ◽  
Jacob J. Schmidt
Keyword(s):  
Ion Channel ◽  
Lipid Bilayer ◽  
Bilayer Formation

scholarly journals Is Lipid Bilayer Binding a Common Property of Inhibitor Cysteine Knot Ion-Channel Blockers?

2007 ◽  
Vol 93 (4) ◽  
pp. L20-L22 ◽  
Author(s):  
Yevgen O. Posokhov ◽  
Philip A. Gottlieb ◽  
Michael J. Morales ◽  
Frederick Sachs ◽  
Alexey S. Ladokhin
Keyword(s):  
Ion Channel ◽  
Lipid Bilayer ◽  
Common Property ◽  
Channel Blockers ◽  
Ion Channel Blockers
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