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Contribution of residues in second transmembrane domain of ASIC1a protein to ion selectivity.
Carattino MD
,
Della Vecchia MC
.
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Acid-sensing ion channels (ASICs) are proton-gated cation-selective channels expressed in the peripheral and central nervous systems. The ion permeation pathway of ASIC1a is defined by residues 426-450 in the second transmembrane (TM2) segment. The gate, formed by the intersection of the TM2 segments, localizes near the extracellular boundary of the plasma membrane. We explored the contribution to ion permeation and selectivity of residues in the TM2 segment of ASIC1a. Studies of accessibility with positively charged methanethiosulfonate reagents suggest that the permeation pathway in the open state constricts below the gate, restricting the passage to large ions. Substitution of residues in the intracellular vestibule at positions 437, 438, 443, or 446 significantly increased the permeability to K(+) versus Na(+). ASIC1a shows a selectivity sequence for alkali metals of Na(+)>Li(+)>K(+)≫Rb(+)>Cs(+). Alanine and cysteine substitutions at position 438 increased, to different extents, the relative permeability to Li(+), K(+), Rb(+), and Cs(+). For these mutants, ion permeation was not a function of the diameter of the nonhydrated ion, suggesting that Gly-438 encompasses an ion coordination site that is essential for ion selectivity. M437C and A443C mutants showed slightly increased permeability to K(+), Rb(+), and Cs(+), suggesting that substitutions at these positions influence ion discrimination by altering molecular sieving. Our results indicate that ion selectivity is accomplished by the contribution of multiple sites in the pore of ASIC1a.
Brown,
Gain-of-function mutations in the MEC-4 DEG/ENaC sensory mechanotransduction channel alter gating and drug blockade.
2007, Pubmed,
Xenbase
Brown,
Gain-of-function mutations in the MEC-4 DEG/ENaC sensory mechanotransduction channel alter gating and drug blockade.
2007,
Pubmed
,
Xenbase
Bässler,
Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
2001,
Pubmed
,
Xenbase
Carattino,
Epithelial Na+ channels are activated by laminar shear stress.
2004,
Pubmed
,
Xenbase
Chen,
Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.
2007,
Pubmed
,
Xenbase
Derebe,
Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites.
2011,
Pubmed
Deval,
Acid-sensing ion channels (ASICs): pharmacology and implication in pain.
2010,
Pubmed
EISENMAN,
Cation selective glass electrodes and their mode of operation.
1962,
Pubmed
Garty,
Characteristics and regulatory mechanisms of the amiloride-blockable Na+ channel.
1988,
Pubmed
Garty,
Epithelial sodium channels: function, structure, and regulation.
1997,
Pubmed
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Holmgren,
On the use of thiol-modifying agents to determine channel topology.
1996,
Pubmed
,
Xenbase
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Karlin,
Substituted-cysteine accessibility method.
1998,
Pubmed
Kashlan,
On the interaction between amiloride and its putative alpha-subunit epithelial Na+ channel binding site.
2005,
Pubmed
,
Xenbase
Kellenberger,
Permeability properties of ENaC selectivity filter mutants.
2001,
Pubmed
,
Xenbase
Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed
Kellenberger,
An external site controls closing of the epithelial Na+ channel ENaC.
2002,
Pubmed
,
Xenbase
Kellenberger,
A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving.
1999,
Pubmed
,
Xenbase
Kellenberger,
On the molecular basis of ion permeation in the epithelial Na+ channel.
1999,
Pubmed
,
Xenbase
Li,
Asymmetric organization of the pore region of the epithelial sodium channel.
2003,
Pubmed
,
Xenbase
Li,
Asp433 in the closing gate of ASIC1 determines stability of the open state without changing properties of the selectivity filter or Ca2+ block.
2011,
Pubmed
,
Xenbase
Li,
Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1.
2011,
Pubmed
,
Xenbase
Läuger,
Microscopic calculation of ion-transport rates in membrane channels.
1982,
Pubmed
Meltzer,
Heteromeric assembly of acid-sensitive ion channel and epithelial sodium channel subunits.
2007,
Pubmed
Palmer,
Voltage-dependent block by amiloride and other monovalent cations of apical Na channels in the toad urinary bladder.
1984,
Pubmed
Palmer,
Interactions of amiloride and other blocking cations with the apical Na channel in the toad urinary bladder.
1985,
Pubmed
Palmer,
Interactions of amiloride and small monovalent cations with the epithelial sodium channel. Inferences about the nature of the channel pore.
1989,
Pubmed
Passero,
Conformational changes associated with proton-dependent gating of ASIC1a.
2009,
Pubmed
,
Xenbase
Pfister,
A gating mutation in the internal pore of ASIC1a.
2006,
Pubmed
,
Xenbase
Schild,
Identification of amino acid residues in the alpha, beta, and gamma subunits of the epithelial sodium channel (ENaC) involved in amiloride block and ion permeation.
1997,
Pubmed
,
Xenbase
Sheng,
Characterization of the selectivity filter of the epithelial sodium channel.
2000,
Pubmed
,
Xenbase
Sheng,
Epithelial sodium channel pore region. structure and role in gating.
2001,
Pubmed
,
Xenbase
Snyder,
Gating induces a conformational change in the outer vestibule of ENaC.
2000,
Pubmed
,
Xenbase
Snyder,
A pore segment in DEG/ENaC Na(+) channels.
1999,
Pubmed
Tolino,
Insights into the mechanism of pore opening of acid-sensing ion channel 1a.
2011,
Pubmed
,
Xenbase
Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase
Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed
Wemmie,
Acid-sensing ion channels: advances, questions and therapeutic opportunities.
2006,
Pubmed
Zhang,
Localization of the pH gate in Kir1.1 channels.
2006,
Pubmed
,
Xenbase
