scholarly journals A flexible GAS belt responds to pore mutations changing the ion selectivity of proton-gated channels

2021 ◽  
Vol 154 (1) ◽  
Author(s):  
Zhuyuan Chen ◽  
Sheng Lin ◽  
Tianze Xie ◽  
Jin-Ming Lin ◽  
Cecilia M. Canessa

Proton-gated ion channels conduct mainly Na+ to induce postsynaptic membrane depolarization. Finding the determinants of ion selectivity requires knowledge of the pore structure in the open conformation, but such information is not yet available. Here, the open conformation of the hASIC1a channel was computationally modeled, and functional effects of pore mutations were analyzed in light of the predicted structures. The open pore structure shows two constrictions of similar diameter formed by the backbone of the GAS belt and, right beneath it, by the side chains of H28 from the reentrant loop. Models of nonselective mutant channels, but not those that maintain ion selectivity, predict enlargement of the GAS belt, suggesting that this motif is quite flexible and that the loss of stabilizing interactions in the central pore leads to changes in size/shape of the belt. Our results are consistent with the “close-fit” mechanism governing selectivity of hASIC1a, wherein the backbone of the GAS substitutes at least part of the hydration shell of a permeant ion to enable crossing the pore constriction.

Author(s):  
Juan J. Nogueira ◽  
Ben Corry

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.


2009 ◽  
Vol 134 (2) ◽  
pp. 151-164 ◽  
Author(s):  
Juan Ramón Martínez-François ◽  
Yanping Xu ◽  
Zhe Lu

Activity of cyclic nucleotide–gated (CNG) cation channels underlies signal transduction in vertebrate visual receptors. These highly specialized receptor channels open when they bind cyclic GMP (cGMP). Here, we find that certain mutations restricted to the region around the ion selectivity filter render the channels essentially fully voltage gated, in such a manner that the channels remain mostly closed at physiological voltages, even in the presence of saturating concentrations of cGMP. This voltage-dependent gating resembles the selectivity filter-based mechanism seen in KcsA K+ channels, not the S4-based mechanism of voltage-gated K+ channels. Mutations that render CNG channels gated by voltage loosen the attachment of the selectivity filter to its surrounding structure, thereby shifting the channel's gating equilibrium toward closed conformations. Significant pore opening in mutant channels occurs only when positive voltages drive the pore from a low-probability open conformation toward a second open conformation to increase the channels' open probability. Thus, the structure surrounding the selectivity filter has evolved to (nearly completely) suppress the expression of inherent voltage-dependent gating of CNGA1, ensuring that the binding of cGMP by itself suffices to open the channels at physiological voltages.


RSC Advances ◽  
2014 ◽  
Vol 4 (48) ◽  
pp. 25195-25200 ◽  
Author(s):  
Limei Wang ◽  
Jianhua Zhu ◽  
Jifu Zheng ◽  
Suobo Zhang ◽  
Liyan dou

The electrospun nanofiber mats revealed high porosity and an interconnected open pore structure. The nanofibers are clearly visible and uniform throughout the composite membrane, which was completely pore-filled.


2000 ◽  
Vol 88 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Todd A. McBride ◽  
Bradley W. Stockert ◽  
Fredric A. Gorin ◽  
Richard C. Carlsen

We tested the hypothesis that eccentric contractions activate mechanosensitive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance. Resting membrane potentials and contractile function were measured in rat tibialis anterior muscles after single or multiple exposures to a series of eccentric contractions. Each exposure produced a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers. The magnitude and duration of the depolarization were related to the number of contractions. Membrane depolarization was due primarily to an increase in Na+ influx, because the estimated Na+-to-K+ permeability ratio was increased in exercised muscles and resting membrane potentials could be partially repolarized by substituting an impermeant cation for extracellular Na+ concentration. Neither the Na+/H+ antiport inhibitor amiloride nor the fast Na+ channel blocker TTX had a significant effect on the depolarization. In contrast, addition of either of two nonselective SAC inhibitors, streptomycin or Gd3+, produced significant membrane repolarization. The results suggest that muscle fibers experience prolonged depolarization after eccentric contractions due, principally, to the activation of Na+-selective SAC.


2016 ◽  
Vol 55 (24) ◽  
pp. 6887-6891 ◽  
Author(s):  
Yunyi Gao ◽  
Jennifer E. S. Szymanowski ◽  
Xinyu Sun ◽  
Peter C. Burns ◽  
Tianbo Liu
Keyword(s):  

2014 ◽  
Vol 141 ◽  
pp. 132-143 ◽  
Author(s):  
Valeria M. Nurchi ◽  
Guido Crisponi ◽  
Massimiliano Arca ◽  
Miriam Crespo-Alonso ◽  
Joanna I. Lachowicz ◽  
...  

2016 ◽  
Vol 128 (24) ◽  
pp. 7001-7005 ◽  
Author(s):  
Yunyi Gao ◽  
Jennifer E. S. Szymanowski ◽  
Xinyu Sun ◽  
Peter C. Burns ◽  
Tianbo Liu
Keyword(s):  

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