scholarly journals Dynamic change of electrostatic field in TMEM16F permeation pathway shifts its ion selectivity

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wenlei Ye ◽  
Tina W Han ◽  
Mu He ◽  
Yuh Nung Jan ◽  
Lily Yeh Jan
Keyword(s):  
Ion Channel ◽  
Electrostatic Field ◽  
Chloride Channels ◽  
Ion Selectivity ◽  
Dynamic Change ◽  
Ion Permeability ◽  
Permeability Ratio ◽  
Phospholipid Scramblase ◽  
A Charge ◽  
Small Conductance

TMEM16F is activated by elevated intracellular Ca2+, and functions as a small-conductance ion channel and as a phospholipid scramblase. In contrast to its paralogs, the TMEM16A/B calcium-activated chloride channels, mouse TMEM16F has been reported as a cation-, anion-, or non-selective ion channel, without a definite conclusion. Starting with the Q559K mutant that shows no current rundown and less outward rectification in excised patch, we found that the channel shifted its ion selectivity in response to the change of intracellular Ca2+ concentration, with an increased permeability ratio of Cl- to Na+ (PCl-/PNa+) at a higher Ca2+ level. The gradual shift of relative ion permeability did not correlate with the channel activation state. Instead, it was indicative of an alteration of electrostatic field in the permeation pathway. The dynamic change of ion selectivity suggests a charge-screening mechanism for TMEM16F ion conduction, and it provides hints to further studies of TMEM16F physiological functions.

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

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.

scholarly journals Molecular Dynamics Simulation of Transmembrane Transport of Chloride Ions in Mutants of Channelrhodopsin

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 852
Author(s):  
Wenying Zhang ◽  
Ting Yang ◽  
Shuangyan Zhou ◽  
Jie Cheng ◽  
Shuai Yuan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Potential Of Mean Force ◽  
Chloride Ions ◽  
Dynamics Simulation ◽  
Mutant Proteins ◽  
Transmembrane Channel ◽  
Anion Conduction

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.

Chloride channels in apical membrane of primary cultures of rabbit distal bright convoluted tubule

1994 ◽  
Vol 266 (4) ◽  
pp. F543-F553 ◽  
Author(s):  
V. Poncet ◽  
M. Tauc ◽  
M. Bidet ◽  
P. Poujeol
Keyword(s):  
Chloride Channels ◽  
Apical Membrane ◽  
Primary Cultures ◽  
Transmembrane Conductance Regulator ◽  
Patch Clamp Technique ◽  
Cl Channel ◽  
Current Voltage ◽  
Cl Channels ◽  
Inside Out ◽  
Small Conductance

Using the patch clamp technique on the apical membrane of primary cultures of rabbit distal bright convoluted tubule cells (DCTb), two types of Cl- channel were identified. A small channel of 9 pS was observed in 9% of the patches. Cells pretreated with 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or 5 microM forskolin increased the expression of Cl- channels by 26 and 37%, respectively. In cell-attached and excised inside-out patches, the current-voltage (I-V) relationships of the 9-pS channel were linear. In only 1 out of 47 active patches was the small-conductance Cl- channel still active 1 h after membrane excision. The addition of 0.1 microM of the catalytic subunit protein kinase A with 2 mM ATP to the cytoplasmic side restored channel activity in 8 out of 15 excised membrane patches. In 5 out of 467 patches of stimulated or nonstimulated cells, a larger Cl- conductance of 30 pS was also recorded. In excised inside-out patches this channel outwardly rectified and was activated by strong depolarization. In cultured DCTb cells, the small-conductance, cAMP-activated Cl- channel shares many properties with the cystic fibrosis transmembrane conductance regulator. Our results suggest that at least the small-conductance channel may participate in Cl- secretion across the apical membrane of DCTb in primary culture. This secretion may increase the rate of the apical Cl-/HCO3- exchange indirectly by enhancing the inwardly-directed Cl- gradient.

Depletion of intracellular Ca2+ stores activates a Ca(2+)-selective channel in vascular endothelium

1994 ◽  
Vol 267 (4) ◽  
pp. C920-C925 ◽  
Author(s):  
L. Vaca ◽  
D. L. Kunze
Keyword(s):  
Vascular Endothelium ◽  
Reversal Potential ◽  
Inward Rectification ◽  
Ion Permeability ◽  
Channel Activity ◽  
Permeability Ratio ◽  
Extracellular Solution ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Selective Channel

The present study was designed to identify the channel responsible for Ca2+ influx after depletion of intracellular Ca2+ stores. Different maneuvers that deplete intracellular Ca2+ stores activated a Ca(2+)-selective channel. Superfusion of single bovine aortic endothelial cells with 50 nmol/l bradykinin, 10 mumol/l ATP, or 10 mumol/l 2,5-di(tert-butyl)-1,4-benzohydroquinone produced activation of channels of the same amplitude in cell-attached patches. Channel activity declined within the first minute after patch excision. The channel showed strong inward rectification and a reversal potential of 0 mV in symmetrical sodium sulfate (Na2SO4) solution. Under these conditions, the conductance was 5 pS in the inward direction. Addition of 10 mmol/l Ca2+ to the extracellular solution shifted the reversal potential to +30 +/- 5 mV, and the conductance for inward current was 11 pS. The reversal potential was used to calculate an ion permeability ratio of Ca2+/Na+ > 10:1.

Ion Channel Permeation and Selectivity

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.

scholarly journals Small conductance chloride channels in the apical membrane of thyroid cells

FEBS Letters ◽  
1990 ◽  
Vol 259 (2) ◽  
pp. 263-268 ◽  
Author(s):  
G. Champigny ◽  
B. Verrier ◽  
C. Gérard ◽  
J. Mauchamp ◽  
M. Lazdunski
Keyword(s):  
Chloride Channels ◽  
Apical Membrane ◽  
Thyroid Cells ◽  
Small Conductance

An ultra-high ion selective hybrid proton exchange membrane incorporated with zwitterion-decorated graphene oxide for vanadium redox flow batteries

2019 ◽  
Vol 7 (20) ◽  
pp. 12669-12680 ◽  
Author(s):  
Yuxia Zhang ◽  
Haixia Wang ◽  
Bo Liu ◽  
Jingli Shi ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Proton Exchange Membrane ◽  
Ion Selectivity ◽  
Proton Exchange ◽  
Hybrid Membranes ◽  
Ion Permeability ◽  
Redox Flow Batteries ◽  
Good Trade ◽  
Exchange Membrane ◽  
Vanadium Redox ◽  
Vanadium Ion

A good trade-off effect between proton conductivity and vanadium ion permeability contributing ultra-high ion selectivity is demonstrated for SPEEK/ZC-GO hybrid membranes influenced by zwitterionic ZC-GO nanofillers.

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