Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :29782492
Publication Date : //

Molecular basis of inhibition of acid sensing ion channel 1A by diminazene.


Acid-sensing ion channels (ASICs) are trimeric proton-gated cation permeable ion channels expressed primarily in neurons. Here we employed site-directed mutagenesis and electrophysiology to investigate the mechanism of inhibition of ASIC1a by diminazene. This compound inhibits mouse ASIC1a with a half-maximal inhibitory concentration (IC50) of 2.4 μM. At first, we examined whether neutralizing mutations of Glu79 and Glu416 alter diminazene block. These residues form a hexagonal array in the lower palm domain that was previously shown to contribute to pore opening in response to extracellular acidification. Significantly, single Gln substitutions at positions 79 and 416 in ASIC1a reduced diminazene apparent affinity by 6-7 fold. This result suggests that diminazene inhibits ASIC1a in part by limiting conformational rearrangement in the lower palm domain. Because diminazene is charged at physiological pHs, we assessed whether it inhibits ASIC1a by blocking the ion channel pore. Consistent with the notion that diminazene binds to a site within the membrane electric field, diminazene block showed a strong dependence with the membrane potential. Moreover, a Gly to Ala mutation at position 438, in the ion conduction pathway of ASIC1a, increased diminazene IC50 by one order of magnitude and eliminated the voltage dependence of block. Taken together, our results indicate that the inhibition of ASIC1a by diminazene involves both allosteric modulation and blocking of ion flow through the conduction pathway. Our findings provide a foundation for the development of more selective and potent ASIC pore blockers.

Authors : Krauson Aram J , Rooney James G , Carattino Marcelo D ,

Related products :

Catalog number Product name Quantity
18-003-42628 Amiloride-sensitive cation channel 3 - Acid-sensing ion channel 3; ASIC3; hASIC3; Testis sodium channel 1; hTNaC1 Polyclonal 0.1 mg Protein A
E1049r Rat ELISA Kit FOR Acid-sensing ion channel 3 96T
ASIC2_RAT Rat ELISA Kit FOR Acid-sensing ion channel 2 96T
E1438m Human ELISA Kit FOR Acid-sensing ion channel 4 96T
ASIC1_CHICK Chicken ELISA Kit FOR Acid-sensing ion channel 1 96T
ASIC3_HUMAN Human ELISA Kit FOR Acid-sensing ion channel 3 96T
abx107921 Polyclonal Rabbit Acid-sensing ion channel 3 Antibody (HRP) 100 μg
abx109482 Polyclonal Rabbit Acid-sensing ion channel 3 Antibody 100 μg
abx106503 Polyclonal Rabbit Acid-sensing ion channel 3 Antibody (FITC) 100 μg
abx105086 Polyclonal Rabbit Acid-sensing ion channel 3 Antibody (Biotin) 100 μg
18-003-43893 Amiloride-sensitive cation channel 4 - Amiloride-sensitive cation channel 4. pituitary; Acid-sensing ion channel 4 Polyclonal 0.05 mg Aff Pur
orb61571 diminazene aceturate diminazene aceturate For research use only. 250 g
28-313 Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, mediates neuronal inhibition by binding to GABA receptors. The type A GABA receptors are pentameric chloride channel 0.1 mg
18-003-42620 Potassium channel subfamily K member 3 - Acid-sensitive potassium channel protein TASK-1; TWIK-related acid-sensitive K(+) channel 1; Two pore potassium channel KT3.1 Polyclonal 0.1 mg Protein A
28-314 The protein encoded by CACNB1 belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, 0.05 mg
28-221 The protein encoded by CACNB1 belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, 0.05 mg
EIAAB31954 ACP1,Adipocyte acid phosphatase,Homo sapiens,Human,LMW-PTP,LMW-PTPase,Low molecular weight cytosolic acid phosphatase,Low molecular weight phosphotyrosine protein phosphatase,Red cell acid phosphatase
28-224 CACNB4 is a member of the beta subunit family, a protein in the voltage-dependent calcium channel complex. CACNB4 plays an important role in calcium channel function by modulating G protein inhibition 0.05 mg
18-003-43175 Potassium channel subfamily K member 5 - Acid-sensitive potassium channel protein TASK-2; TWIK-related acid-sensitive K(+) channel 2 Polyclonal 0.05 mg Aff Pur
orb80743 Melanotan-II protein The molecular formula is C50H69N15O9. It has the amino acid sequence of Ac-Nle-cyclo [Asp-His-D-Phe-Arg-Trp-Lys]-NH2 and molecular weight of 1024.2 Dalton. The CAS Number is 12106 20 mg
31-103 GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the gaba_benzodiazepine receptor and opening an integral chloride channel. 0.1 mg
31-102 GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the gaba_benzodiazepine receptor and opening an integral chloride channel. 0.1 mg
31-134 GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the gaba_benzodiazepine receptor and opening an integral chloride channel. 0.1 mg
536-71-0 Diminazene Diminazene 1g
orb81085 Eledoisin protein Eledoisin's molecular weight is 1188.4 having an amino acid sequence of Glp-Pro-Ser-Lys-Asp-Ala-Phe-Ile-Gly-Leu-Met-NH2 and a molecular formula of C54H85N13O15S. For research use onl 5 mg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur