Artículo

Plazas, P.V.; De Rosa, M.J.; Gomez-Casati, M.E.; Verbitsky, M.; Weisstaub, N.; Katz, E.; Bouzat, C.; Elgoyhen, A.B. "Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor" (2005) British Journal of Pharmacology. 145(7):963-974
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Abstract:

We have performed a systematic mutagenesis of three hydrophobic rings (17′, 13′ and 9′) within transmembrane region (TM) 2 of the α9α10 nicotinic cholinergic receptor (nAChR) to a hydrophilic (threonine) residue and compared the properties of mutant receptors reconstituted in Xenopus laevis oocytes. Phenotypic changes in α9α10 mutant receptors were evidenced by a decrease in the desensitization rate, an increase in both the EC 50 for ACh as well as the efficacy of partial agonists and the reduction of the allosteric modulation by extracellular Ca 2+. Mutated receptors exhibited spontaneous openings and, at the single-channel level, an increased apparent mean open time with no major changes in channel conductance, thus suggesting an increase in gating of the channel as the underlying mechanism. Overall, the degrees of the phenotypes of mutant receptors were more overt in the case of the centrally located V13′T mutant. Based on the atomic model of the pore of the electric organ of the Torpedo ray, we can propose that the interactions of side chains at positions 13′ and 9′ are key ones in creating an energetic barrier to ion permeation. In spite of the fact that the roles of the TM2 residues are mostly conserved in the distant α9α10 member of the nAChR family, their mechanistic contributions to channel gating show significant differences when compared to other nAChRs. These differences might be originated from slight differential intramolecular rearrangements during gating for the different receptors and might lead each nAChR to be in tune with their physiological roles. © 2005 Nature Publishing Group All rights reserved.

Registro:

Documento: Artículo
Título:Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor
Autor:Plazas, P.V.; De Rosa, M.J.; Gomez-Casati, M.E.; Verbitsky, M.; Weisstaub, N.; Katz, E.; Bouzat, C.; Elgoyhen, A.B.
Filiación:Institute de Investigaciones en Ingenieria Genetica y Biologia Molecular (INGEBI), CONICET-UBA, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Instituto de Investigaciones Bioquímicas de Bahía Blanca, UNS-CONICET, Bahía Blanca F-8000FWB, Argentina
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Columbia Genome Center, Columbia University, 1150 St Nicholas Ave., New York, NY 10032, United States
Columbia University, 1051 Riverside Drive, New York, NY 10032, United States
Palabras clave:Acetylcholine; Channel gating; Cys-loop receptors; Ionotropic receptors; Nicotinic receptors; nicotinic receptor; partial agonist; tropisetron; animal cell; article; channel gating; controlled study; electric organ; extracellular calcium; hydrophilicity; hydrophobicity; ion transport; membrane potential; nonhuman; phenotype; priority journal; ring opening; Xenopus laevis; Acetylcholine; Allosteric Regulation; Amino Acid Sequence; Animals; Calcium; Cholinergic Agents; Dose-Response Relationship, Drug; Ion Channel Gating; Membrane Potentials; Molecular Sequence Data; Mutagenesis, Site-Directed; Oocytes; Patch-Clamp Techniques; Phenotype; Protein Subunits; Receptors, Nicotinic; Recombinant Proteins; Sequence Alignment; Transfection; Xenopus laevis
Año:2005
Volumen:145
Número:7
Página de inicio:963
Página de fin:974
DOI: http://dx.doi.org/10.1038/sj.bjp.0706224
Título revista:British Journal of Pharmacology
Título revista abreviado:Br. J. Pharmacol.
ISSN:00071188
CODEN:BJPCB
CAS:tropisetron, 89565-68-4; Acetylcholine, 51-84-3; Calcium, 7440-70-2; Cholinergic Agents; Chrna9 protein, rat; Protein Subunits; Receptors, Nicotinic; Recombinant Proteins; alpha10 acetylcholine receptor, rat
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00071188_v145_n7_p963_Plazas

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Citas:

---------- APA ----------
Plazas, P.V., De Rosa, M.J., Gomez-Casati, M.E., Verbitsky, M., Weisstaub, N., Katz, E., Bouzat, C.,..., Elgoyhen, A.B. (2005) . Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor. British Journal of Pharmacology, 145(7), 963-974.
http://dx.doi.org/10.1038/sj.bjp.0706224
---------- CHICAGO ----------
Plazas, P.V., De Rosa, M.J., Gomez-Casati, M.E., Verbitsky, M., Weisstaub, N., Katz, E., et al. "Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor" . British Journal of Pharmacology 145, no. 7 (2005) : 963-974.
http://dx.doi.org/10.1038/sj.bjp.0706224
---------- MLA ----------
Plazas, P.V., De Rosa, M.J., Gomez-Casati, M.E., Verbitsky, M., Weisstaub, N., Katz, E., et al. "Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor" . British Journal of Pharmacology, vol. 145, no. 7, 2005, pp. 963-974.
http://dx.doi.org/10.1038/sj.bjp.0706224
---------- VANCOUVER ----------
Plazas, P.V., De Rosa, M.J., Gomez-Casati, M.E., Verbitsky, M., Weisstaub, N., Katz, E., et al. Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor. Br. J. Pharmacol. 2005;145(7):963-974.
http://dx.doi.org/10.1038/sj.bjp.0706224