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Abstract:

Studies of the electrophysiological response to acetylcholine (ACh) in mammalian outer hair cells (OHCs) are hindered by the presence of a large potassium current, IK,n, most likely mediated by channels containing the KCNQ4 subunit. Since IK,n can be blocked by linopirdine, cholinergic effects might be better revealed in the presence of this compound. The aim of the present work was to study the effects of linopirdine on the ACh-evoked responses through α9α10-containing native and recombinant nicotinic cholinergic receptors. Responses to ACh were blocked by linopirdine in both OHCs and inner hair cells (IHCs) of rats at postnatal days 21-27 (OHCs) and 9-11 (IHCs). In addition, linopirdine blocked responses of recombinant α9α10 nicotinic cholinergic receptors (nAChRs) in a concentration-dependent manner with an IC50 of 5.2 μM. Block by linopirdine was readily reversible, voltage independent, and surmountable at high concentrations of ACh, thus suggestive of a competitive type of interaction with the receptor. The present results contribute to the pharmacological characterization of α9α10-containing nicotinic receptors and indicate that linopirdine should be used with caution when analyzing the cholinergic sensitivity of cochlear hair cells.

Registro:

Documento: Artículo
Título:Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells
Autor:Gomez-Casati, M.E.; Katz, E.; Glowatzki, E.; Lioudyno, M.I.; Fuchs, P.; Elgoyhen, A.B.
Filiación:Inst. Invest. Ing. Genet./Biol. M., Consejo Nac. de Invest. Cie. y Tec., Buenos Aires 1428, Argentina
Departamento de Biología, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Center for Hearing and Balance, Dept. Otolaryngol.-Head/Neck Surg., Johns Hopkins Univ. Sch. of Medicine, Baltimore, MD 21205-2195, United States
Inst. Invest. Ing. Genet./Biol. M., Vuelta de Obligada 2490, 1428 Buenos Aires, Argentina
Palabras clave:Acetylcholine; Ion channels; K+ channels; Linopirdine; Nicotinic receptors; acetylcholine; linopirdine; nicotinic receptor; potassium; potassium channel; acetylcholine; alpha10 acetylcholine receptor, rat; Chrna9 protein, rat; indole derivative; linopirdine; nicotinic receptor; potassium channel blocking agent; protein subunit; pyridine derivative; recombinant protein; animal cell; animal tissue; article; cochlea; concentration response; hair cell; newborn; nonhuman; priority journal; rat; Xenopus laevis; animal; cell membrane potential; drug effect; gene expression; genetics; metabolism; oocyte; patch clamp; physiology; Sprague Dawley rat; Acetylcholine; Animals; Gene Expression; Hair Cells, Outer; Indoles; Membrane Potentials; Oocytes; Patch-Clamp Techniques; Potassium Channel Blockers; Protein Subunits; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Recombinant Proteins; Xenopus laevis
Año:2004
Volumen:5
Número:3
Página de inicio:261
Página de fin:269
DOI: http://dx.doi.org/10.1007/s10162-004-4025-6
Título revista:JARO - Journal of the Association for Research in Otolaryngology
Título revista abreviado:JARO J. Assoc. Res. Otolaryngol.
ISSN:15253961
CODEN:JJARB
CAS:acetylcholine, 51-84-3, 60-31-1, 66-23-9; linopirdine, 105431-72-9; potassium, 7440-09-7; Acetylcholine, 51-84-3; alpha10 acetylcholine receptor, rat; Chrna9 protein, rat; Indoles; linopirdine, 105431-72-9; Potassium Channel Blockers; Protein Subunits; Pyridines; Receptors, Nicotinic; Recombinant Proteins
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_15253961_v5_n3_p261_GomezCasati.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15253961_v5_n3_p261_GomezCasati

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Citas:

---------- APA ----------
Gomez-Casati, M.E., Katz, E., Glowatzki, E., Lioudyno, M.I., Fuchs, P. & Elgoyhen, A.B. (2004) . Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells. JARO - Journal of the Association for Research in Otolaryngology, 5(3), 261-269.
http://dx.doi.org/10.1007/s10162-004-4025-6
---------- CHICAGO ----------
Gomez-Casati, M.E., Katz, E., Glowatzki, E., Lioudyno, M.I., Fuchs, P., Elgoyhen, A.B. "Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells" . JARO - Journal of the Association for Research in Otolaryngology 5, no. 3 (2004) : 261-269.
http://dx.doi.org/10.1007/s10162-004-4025-6
---------- MLA ----------
Gomez-Casati, M.E., Katz, E., Glowatzki, E., Lioudyno, M.I., Fuchs, P., Elgoyhen, A.B. "Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells" . JARO - Journal of the Association for Research in Otolaryngology, vol. 5, no. 3, 2004, pp. 261-269.
http://dx.doi.org/10.1007/s10162-004-4025-6
---------- VANCOUVER ----------
Gomez-Casati, M.E., Katz, E., Glowatzki, E., Lioudyno, M.I., Fuchs, P., Elgoyhen, A.B. Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells. JARO J. Assoc. Res. Otolaryngol. 2004;5(3):261-269.
http://dx.doi.org/10.1007/s10162-004-4025-6