Characterising the Ion Selectivity and Calcium Permeability of the Erwinia Ligand-Gated Ion Channel

Channelrhodopsins (ChRs) are light-gated transmembrane cation channels which are widely used for optogenetic technology. Replacing glutamate located at the central gate of the ion channel with positively charged amino acid residues will reverse ion selectivity and allow anion conduction. The structures and properties of the ion channel, the transport of chloride, and potential of mean force (PMF) of the chimera protein (C1C2) and its mutants, EK-TC, ER-TC and iChloC, were investigated by molecular dynamics simulation. The results show that the five-fold mutation in E122Q-E129R-E140S-D195N-T198C (iChloC) increases the flexibility of the transmembrane channel protein better than the double mutations in EK-TC and ER-TC, and results in an expanded ion channel pore size and decreased steric resistance. The iChloC mutant was also found to have a higher affinity for chloride ions and, based on surface electrostatic potential analysis, provides a favorable electrostatic environment for anion conduction. The PMF free energy curves revealed that high affinity Cl− binding sites are generated near the central gate of the three mutant proteins. The energy barriers for the EK-TC and ER-TC were found to be much higher than that of iChloC. The results suggest that the transmembrane ion channel of iChloC protein is better at facilitating the capture and transport of chloride ions.

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Ion Channel Permeation and Selectivity

The Oxford Handbook of Neuronal Ion Channels ◽

10.1093/oxfordhb/9780190669164.013.22 ◽

2019 ◽

Author(s):

Juan J. Nogueira ◽

Ben Corry

Keyword(s):

Ion Channels ◽

Ion Channel ◽

Ion Selectivity ◽

Ionic Currents ◽

Biological Processes ◽

Ion Permeation ◽

Voltage Gated ◽

Physical Mechanisms ◽

Theoretical Approaches ◽

Mechanistic Insight

Many biological processes essential for life rely on the transport of specific ions at specific times across cell membranes. Such exquisite control of ionic currents, which is regulated by protein ion channels, is fundamental for the proper functioning of the cells. It is not surprising, therefore, that the mechanism of ion permeation and selectivity in ion channels has been extensively investigated by means of experimental and theoretical approaches. These studies have provided great mechanistic insight but have also raised new questions that are still unresolved. This chapter first summarizes the main techniques that have provided significant knowledge about ion permeation and selectivity. It then discusses the physical mechanisms leading to ion permeation and the explanations that have been proposed for ion selectivity in voltage-gated potassium, sodium, and calcium channels.

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ENaC structure and function in the wake of a resolved structure of a family member

AJP Renal Physiology ◽

10.1152/ajprenal.00259.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. F684-F696 ◽

Cited By ~ 89

Author(s):

Ossama B. Kashlan ◽

Thomas R. Kleyman

Keyword(s):

Plasma Membrane ◽

Ion Channel ◽

Functional Data ◽

Ion Selectivity ◽

External Environment ◽

Structure And Function ◽

Close Proximity ◽

Channel Assembly ◽

And Function ◽

Insight Into

Our understanding of epithelial Na+ channel (ENaC) structure and function has been profoundly impacted by the resolved structure of the homologous acid-sensing ion channel 1 (ASIC1). The structure of the extracellular and pore regions provide insight into channel assembly, processing, and the ability of these channels to sense the external environment. The absence of intracellular structures precludes insight into important interactions with intracellular factors that regulate trafficking and function. The primary sequences of ASIC1 and ENaC subunits are well conserved within the regions that are within or in close proximity to the plasma membrane, but poorly conserved in peripheral domains that may functionally differentiate family members. This review examines functional data, including ion selectivity, gating, and amiloride block, in light of the resolved ASIC1 structure.

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Conversion of the Ion Selectivity of the 5-HT3AReceptor from Cationic to Anionic Reveals a Conserved Feature of the Ligand-gated Ion Channel Superfamily

Journal of Biological Chemistry ◽

10.1074/jbc.m009575200 ◽

2001 ◽

Vol 276 (14) ◽

pp. 10977-10983 ◽

Cited By ~ 99

Author(s):

Martin J. Gunthorpe ◽

Sarah C. R. Lummis

Keyword(s):

Ion Channel ◽

Ion Selectivity

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Electrostatic Effects on Ion Selectivity and Rectification in Designed Ion Channel Peptides

Journal of the American Chemical Society ◽

10.1021/ja9629672 ◽

1997 ◽

Vol 119 (14) ◽

pp. 3212-3217 ◽

Cited By ~ 51

Author(s):

J. D. Lear ◽

J. P. Schneider ◽

P. K. Kienker ◽

W. F. DeGrado

Keyword(s):

Ion Channel ◽

Ion Selectivity ◽

Electrostatic Effects

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Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny

Stem Cells International ◽

10.1155/2013/784629 ◽

2013 ◽

Vol 2013 ◽

pp. 1-25 ◽

Cited By ~ 6

Author(s):

Leonhard Linta ◽

Marianne Stockmann ◽

Qiong Lin ◽

André Lechel ◽

Christian Proepper ◽

...

Keyword(s):

Ion Channels ◽

Ion Channel ◽

Ion Selectivity ◽

Expression Patterns ◽

Stem Cell Differentiation ◽

Human Keratinocytes ◽

Ips Cells ◽

Cellular Processes ◽

Gating Mechanism ◽

Channel Expression

Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. Additionally, iPSCs express a much higher number of ion channels compared to keratinocytes. Further, to narrow down specificity of ion channel expression in iPS cells we compared their expression patterns with differentiated progeny, namely, neurons and cardiomyocytes derived from iPS cells. To conclude, hiPSCs exhibit a very considerable and diverse ion channel expression pattern. Their detailed analysis could give an insight into their contribution to many cellular processes and even disease mechanisms.

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Dynamic Change of Electrostatic Field in TMEM16F Permeation Pathway Shifts Its Ion Selectivity

10.1101/515569 ◽

2019 ◽

Author(s):

Wenlei Ye ◽

Tina W. Han ◽

Mu He ◽

Yuh Nung Jan ◽

Lily Y. Jan

Keyword(s):

Membrane Potential ◽

Ion Channel ◽

Electrostatic Field ◽

Positive Feedback ◽

Ion Selectivity ◽

Dynamic Change ◽

Divalent Ions ◽

Phospholipid Scramblase ◽

Intracellular Ca ◽

Small Conductance

AbstractTMEM16F is activated by elevated intracellular Ca2+, and functions both as a small-conductance ion channel permeable to Ca2+ and as a phospholipid scramblase. It is important to hold this positive feedback in check to prevent prolonged Ca2+-overloading in cells. We hypothesize that TMEM16F shifts its ion selectivity so that it is more permeable to Cl− than cations at high intracellular Ca2+ concentration. We tested this hypothesis with the Q559K mutant that shows no current rundown in excised patch with prolonged Ca2+ elevation. Recorded in NaCl−based solution, the channel shifted its ion selectivity from Na+-selective to Cl−-selective when intracellular Ca2+ was increased. The ion selectivity switch did not correlate with changes of channel open state. Rather, it was indicative of an alteration of electrostatic field in the permeation pathway. Shifting ion-selectivity synergistically by intracellular divalent ions and membrane potential could work as a built-in mechanism that allows TMEM16F to brake the positive feedback.

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Competition among Ca2+, Mg2+, and Na+ for Model Ion Channel Selectivity Filters: Determinants of Ion Selectivity

The Journal of Physical Chemistry B ◽

10.1021/jp304925a ◽

2012 ◽

Vol 116 (35) ◽

pp. 10703-10714 ◽

Cited By ~ 33

Author(s):

Todor Dudev ◽

Carmay Lim

Keyword(s):

Ion Channel ◽

Ion Selectivity ◽

Channel Selectivity ◽

Ion Channel Selectivity

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Ion selectivity and activation of the M2 ion channel of influenza virus

Biophysical Journal ◽

10.1016/s0006-3495(96)79690-x ◽

1996 ◽

Vol 70 (3) ◽

pp. 1335-1346 ◽

Cited By ~ 105

Author(s):

K. Shimbo ◽

D.L. Brassard ◽

R.A. Lamb ◽

L.H. Pinto

Keyword(s):

Influenza Virus ◽

Ion Channel ◽

Ion Selectivity

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Quantum Mechanical Coherence of K+ Ion Wave Packets Increases Conduction in the KcsA Ion Channel

Applied Sciences ◽

10.3390/app10124250 ◽

2020 ◽

Vol 10 (12) ◽

pp. 4250

Author(s):

Johann Summhammer ◽

Georg Sulyok ◽

Gustav Bernroider

Keyword(s):

Ion Channel ◽

Force Fields ◽

Quantum Effect ◽

Ion Selectivity ◽

Wave Packets ◽

Thermal Fluctuations ◽

Carbonyl Oxygen ◽

Atomic Scale ◽

Quantum Mechanical ◽

Time Pattern

We simulate the transmission of K+ ions through the KcsA potassium ion channel filter region at physiological temperatures, employing classical molecular dynamics (MD) at the atomic scale together with a quantum mechanical version of MD simulation (QMD), treating single ions as quantum wave packets. We provide a direct comparison between both concepts, embedding the simulations into identical force fields and thermal fluctuations. The quantum simulations permit the estimation of coherence times and wave packet dispersions of a K+ ion over a range of 0.5 nm (a range that covers almost 50% of the filter domains longitudinal extension). We find that this observed extension of particle delocalization changes the mean orientation of the coordinating carbonyl oxygen atoms significantly, transiently suppressing their ‘caging action’ responsible for selective ion coordination. Compared to classical MD simulations, this particular quantum effect allows the K+ ions to ‘escape’ more easily from temporary binding sites provided by the surrounding filter atoms. To further elucidate the role of this observation for ion conduction rates, we compare the temporal pattern of single conduction events between classical MD and quantum QMD simulations at a femto-sec time scale. A finding from both approaches is that ion permeation follows a very irregular time pattern, involving flushes of permeation interrupted by non-conductive time intervals. However, as compared with classical behavior, the QMD simulation shortens non-conductive time by more than a half. As a consequence, and given the same force-fields, the QMD-simulated ion current appears to be considerably stronger as compared with the classical current. To bring this result in line with experimentally observed ion currents and the predictions based on Nernst–Planck theories, the conclusion is that a transient short time quantum behavior of permeating ions can successfully compromise high conduction rates with ion selectivity in the filter of channel proteins.

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