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

2019 ◽  
Author(s):  
Gilman Toombes
Keyword(s):  
Electrostatic Field ◽  
Ion Selectivity ◽  
Dynamic Change

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 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 Differential ion dehydration energetics explains selectivity in the non-canonical lysosomal K+ channel TMEM175

2021 ◽  
Author(s):  
SeCheol Oh ◽  
Fabrizio Marinelli ◽  
Wenchang Zhou ◽  
Jooyeon Lee ◽  
Ho Jeong Choi ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Field ◽  
Ion Selectivity ◽  
Selectivity Filter ◽  
K Channel ◽  
Monovalent Cations ◽  
Ion Flow ◽  
Dynamics Simulations ◽  
Channel Structures

Structures of the human lysosomal K+ channel TMEM175 in open and closed states revealed a novel architecture lacking the canonical K+ selectivity filter motif present in previously known K+ channel structures. A hydrophobic constriction composed of four isoleucine residues was resolved in the pore and proposed to serve as the gate in the closed state, and to confer ion selectivity in the open state. Here, we achieve higher-resolution structures of the open and closed states and employ molecular dynamics simulations to analyze the conducting properties of the putative open state, demonstrating that it is capable of permeating K+ ions at the expected rate. Monovalent cations must dehydrate significantly to penetrate the narrow hydrophobic constriction, but ion flow is assisted by a favorable electrostatic field generated by the protein that spans the length of the pore. The balance of these opposing energetic factors explains why permeation is feasible, and why TMEM175 is selective for K+ over Na+, despite the absence of the canonical selectivity filter. Accordingly, mutagenesis experiments reveal an exquisite sensitivity of the channel to perturbations that mitigate the constriction. Together, these data reveal a novel mechanism for selective permeation of ions by TMEM175 that is unlike that of other K+ channels.

Transient Response of Electrostatic Field due to Collision ESD between Spherical Electrodes by using Bare-chip Optical Electric Field Sensor

2020 ◽  
Vol 140 (12) ◽  
pp. 599-600
Author(s):  
Kento Kato ◽  
Ken Kawamata ◽  
Shinobu Ishigami ◽  
Ryuji Osawa ◽  
Takeshi Ishida ◽  
...  
Keyword(s):  
Electric Field ◽  
Transient Response ◽  
Electrostatic Field ◽  
Electric Field Sensor ◽  
Field Sensor

Electrostatic Field Distribution Measurement Using MEMS Micro-mirror Array

2014 ◽  
Vol 134 (12) ◽  
pp. 378-384 ◽  
Author(s):  
Toshihide Kuriyama ◽  
Wataru Takatsuji ◽  
Takaki Itoh ◽  
Hiroshi Maeda ◽  
Toshiyuki Nakaie ◽  
...  
Keyword(s):  
Field Distribution ◽  
Electrostatic Field ◽  
Distribution Measurement

Dynamics of the Davydov Soliton in Electrostatic Field

2006 ◽  
Vol 65 (19) ◽  
pp. 1789-1798
Author(s):  
Y. E. Natanzon ◽  
L.S. Brizhik ◽  
O.O. Yeremko
Keyword(s):  
Electrostatic Field

Determination of clinical efficiency of deproteinized dialysate from blood of milk-fed calves after endoprosthetics in patients with ventral hernias

2020 ◽  
Vol 28 (3) ◽  
pp. 323-333
Author(s):  
Sergej V. Ivanov ◽  
Ilya S. Ivanov ◽  
Evgenij G. Obyedkov ◽  
Liliya P. Popova
Keyword(s):  
Abdominal Wall ◽  
Inflammatory Reaction ◽  
Inflammatory Process ◽  
Anterior Abdominal Wall ◽  
Dynamic Change ◽  
Main Group ◽  
Control Group ◽  
Surgical Department ◽  
Regeneration Stage

Aim. To study the influence of deproteinized dialysate from blood of milk-fed calves on the type of exudative discharge and dynamics of inflammatory reaction after hernia repair with plastics of the anterior abdominal wall with hernioendoprosthesis of polypropylene. Materials and Methods. The study involved 59 patients being on stationary treatment in the surgical department of Kursk Regional Clinical Hospital. Patients were hospitalized for the herniation of small or medium dimension. The patients were divided to two groups: the main (n=30) and control (n=29) groups. After endoprosthetics, the patients of the control group were given complex conservative treatment. The patients of the main group, besides standard treatment, were administered deproteinized dialysate from blood of milk-fed calves intravenously in drips 10 ml + 200 ml of 0.9% sodium chloride solution within 7 days. For cytological examination and determination of the type of cytograms, the traumatic discharge was collected and analyzed using the method of M.F. Kamaev and M.A. Palthsev. Results. Cytomorphometric examination was conducted on the third, fifth and seventh day after endoprosthetics with the aim of studying dynamic changes. Determination of cell composition and also of its changes characteristic of each studied period, was necessary for obtaining further information characterizing inflammatory process in the region of placement of the endoprosthesis. After endoprosthetics in patients who were administered hemodialysate, the inflammatory reaction was less pronounced than in patients who did not receive the preparation. This was associated with a more dynamic change of stages of the inflammatory process. In patients of the main group who received deproteinized dialysate, regenerative type of inflammation first appeared on the fifth day and made 6.9%; by the seventh day the share of patients with the regenerative type rose to 17.5%, while in the patients of the control group no regeneration stage was observed in both periods. Conclusion. Analysis of the efficiency of influence of hemodialysate on the inflammatory reaction in plastics of the anterior abdominal wall with polypropylene endoprosthesis evidences faster course of all stages of inflammation and reduction of its intensity by 10%.

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