A physical mechanism for large-ion selectivity of ion channels

2002 ◽  
Vol 4 (19) ◽  
pp. 4763-4769 ◽  
Author(s):  
Dirk Gillespie ◽  
Wolfgang Nonner ◽  
Douglas Henderson ◽  
Robert S. Eisenberg
Keyword(s):  
Ion Channels ◽  
Physical Mechanism ◽  
Ion Selectivity

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 Thermal Responsive Ion Selectivity of Uranyl Peroxide Nanocages: An Inorganic Mimic of K+ Ion Channels

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

scholarly journals Thermal Responsive Ion Selectivity of Uranyl Peroxide Nanocages: An Inorganic Mimic of K+ Ion Channels

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

scholarly journals Acid-sensing (proton-gated) ion channels (ASICs) in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Stephan Kellenberger ◽  
Lachlan D. Rash
Keyword(s):  
Ion Channels ◽  
Heterologous Expression ◽  
Splice Variants ◽  
Ion Selectivity ◽  
Taste Receptor ◽  
Lung Epithelial Cells ◽  
Na Channel ◽  
Cochlear Hair Cells ◽  
Peripheral Neurons ◽  
Heterologous Expression Systems

Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [45, 2, 3]) are members of a Na+ channel superfamily that includes the epithelial Na+ channel (ENaC), the FMRF-amide activated channel (FaNaC) of invertebrates, the degenerins (DEG) of Caenorhabitis elegans, channels in Drosophila melanogaster and 'orphan' channels that include BLINaC [66] and INaC [68] that have also been named BASICs, for bile acid-activated ion channels [86]. ASIC subunits contain 2 TM domains and assemble as homo- or hetero-trimers [43, 40, 7, 90, 89, 73] to form proton-gated, voltage-insensitive, Na+ permeable, channels that are activated by levels of acidosis occurring in both physiological and pathophysiological conditions with ASIC3 also playing a role in mechanosensation (reviewed in [42, 85, 45, 65, 23]) . Splice variants of ASIC1 [termed ASIC1a (ASIC, ASICα, BNaC2α) [80], ASIC1b (ASICβ, BNaC2β) [19] and ASIC1b2 (ASICβ2) [75]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [termed ASIC2a (MDEG1, BNaC1α, BNC1α) [63, 81, 39] and ASIC2b (MDEG2, BNaC1β) [53]] have been cloned and differ in the first third of the protein. Unlike ASIC2a (listed in table), heterologous expression of ASIC2b alone does not support H+-gated currents. A third member, ASIC3 (DRASIC, TNaC1) [79] is one of the most pH-sensitive isoforms (along with ASIC1a) and has the fastest activation and desensitisation kinetics, however can also carry small sustained currents. ASIC4 (SPASIC) evolved as a proton-sensitive channel but seems to have lost this function in mammals [55]. Mammalian ASIC4 does not support a proton-gated channel in heterologous expression systems but is reported to downregulate the expression of ASIC1a and ASIC3 [1, 41, 33, 51]. ASIC channels are primarily expressed in central (ASIC1a, -2a, 2b and -4) and peripheral neurons including nociceptors (ASIC1-3) where they participate in neuronal sensitivity to acidosis. They have also been detected in taste receptor cells (ASIC1-3)), photoreceptors and retinal cells (ASIC1-3), cochlear hair cells (ASIC1b), testis (hASIC3), pituitary gland (ASIC4), lung epithelial cells (ASIC1a and -3), urothelial cells, adipose cells (ASIC3), vascular smooth muscle cells (ASIC1-3), immune cells (ASIC1,-3 and -4) and bone (ASIC1-3) (ASIC distribution is well reviewed in [52, 27]). A neurotransmitter-like function of protons has been suggested, involving postsynaptically located ASICs of the CNS in functions such as learning and fear perception [34, 47, 93], responses to focal ischemia [87] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [38], as well as seizures [94] and pain [85, 28, 29, 13, 31]. Heterologously expressed heteromultimers form ion channels with differences in kinetics, ion selectivity, pH- sensitivity and sensitivity to blockers that resemble some of the native proton activated currents recorded from neurones [53, 5, 37, 11]. In general, the known small molecule inhibitors of ASICs are non-selective or partially selective, whereas the venom peptide inhibitors have substantially higher selectivity and potency. Several clinically used drugs are known to inhibit ASICs, however they are generally more potent at other targets (e.g. amiloride at ENaCs, ibuprofen at COX enzymes) [64, 60]. The information in the tables below are for the effects of inhibitors on homomeric channels, for information of known effect on heteromeric channels see the comments below.

scholarly journals Conserved His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

2020 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Ion Selectivity ◽  
Fear Memory ◽  
Amino Terminus ◽  
Ion Permeation ◽  
Structural Explanation ◽  
Cryo Electron Microscopy ◽  
Acid Sensing Ion Channels ◽  
And Function

ABSTRACTAcid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here we extract full-length chicken ASIC1a (cASIC1a) from cell membranes using styrene maleic acid (SMA) copolymer, yielding structures of ASIC1a channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1a that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.

scholarly journals Acid-sensing (proton-gated) ion channels (ASICs) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Stephan Kellenberger ◽  
Lachlan D. Rash ◽  
Laurent Schild
Keyword(s):  
Ion Channels ◽  
Heterologous Expression ◽  
Splice Variants ◽  
Ion Selectivity ◽  
Taste Receptor ◽  
Lung Epithelial Cells ◽  
Na Channel ◽  
Cochlear Hair Cells ◽  
Peripheral Neurons ◽  
Heterologous Expression Systems

Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [35]) are members of a Na+ channel superfamily that includes the epithelial Na+ channel (ENaC), the FMRF-amide activated channel (FaNaC) of invertebrates, the degenerins (DEG) of Caenorhabitis elegans, channels in Drosophila melanogaster and 'orphan' channels that include BLINaC [46] and INaC [47] that have also been named BASICs, for bile acid-activated ion channels [58]. ASIC subunits contain two TM domains and assemble as homo- or hetero-trimers [34, 31, 5] to form proton-gated, voltage-insensitive, Na+ permeable, channels (reviewed in [33, 57]). Splice variants of ASIC1 [termed ASIC1a (ASIC, ASICα, BNaC2α) [55], ASIC1b (ASICβ, BNaC2β) [13] and ASIC1b2 (ASICβ2) [50]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [termed ASIC2a (MDEG1, BNaC1α, BNC1α) [45, 56, 30] and ASIC2b (MDEG2, BNaC1β) [40]] have been cloned. Unlike ASIC2a (listed in table), heterologous expression of ASIC2b alone does not support H+-gated currents. A third member, ASIC3 (DRASIC, TNaC1) [54], has been identified. A fourth mammalian member of the family (ASIC4/SPASIC) does not support a proton-gated channel in heterologous expression systems and is reported to downregulate the expression of ASIC1a and ASIC3 [1, 32, 24, 39]. ASIC channels are primarily expressed in central and peripheral neurons including nociceptors where they participate in neuronal sensitivity to acidosis. They have also been detected in taste receptor cells (ASIC1-3), photoreceptors and retinal cells (ASIC1-3), cochlear hair cells (ASIC1b), testis (hASIC3), pituitary gland (ASIC4), lung epithelial cells (ASIC1a and -3), urothelial cells, adipose cells (ASIC3), vascular smooth muscle cells (ASIC1-3), immune cells (ASIC1,-3 and -4) and bone (ASIC1-3). A neurotransmitter-like function of protons has been suggested, involving postsynaptically located ASICs of the CNS in functions such as learning and fear perception [25, 36, 63], responses to focal ischemia [59] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [29], as well as seizures [64] and pain [19, 20, 10, 22]. Heterologously expressed heteromultimers form ion channels with differences in kinetics, ion selectivity, pH- sensitivity and sensitivity to blockers that resemble some of the native proton activated currents recorded from neurones [40, 3, 28, 8].

scholarly journals Molecular Basis for Ion Selectivity in Heteromeric Acid-Sensing Ion Channels

2019 ◽  
Vol 116 (3) ◽  
pp. 110a
Author(s):  
Zeshan P. Sheikh ◽  
Timothy Lynagh ◽  
Emelie Flood ◽  
Celine Boiteux ◽  
Toby W. Allen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Molecular Basis ◽  
Ion Selectivity ◽  
Acid Sensing Ion Channels

Channels and electrical signals

2019 ◽  
pp. 37-56
Author(s):  
Gordon L. Fain
Keyword(s):  
Ion Channels ◽  
Hair Cell ◽  
Ion Selectivity ◽  
Ion Homeostasis ◽  
Membrane Conductance ◽  
Sensory Transduction ◽  
Ionotropic Receptor ◽  
Electrical Signals ◽  
Voltage Clamping ◽  
And Function

“Channels and electrical signals” is the third chapter of the book Sensory Transduction and reviews the structure and function of ion channels, the structure of channel pores, and mechanisms of gating. It introduces ionotropic receptor molecules, which are proteins that function as sensory receptors but are also ion channels, whose gating can produce changes in membrane conductance directly. It then uses the hair cell of the inner ear as an example to introduce the concepts of membrane potentials, the Nernst equation, ion homeostasis, the Goldman voltage equation, and driving force. A description of the technique of voltage clamping follows, together with the application of this technique to the hair cell to explain the method of measuring changes in channel gating and the ion selectivity of channel pores.

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