Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells
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...
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| Formato: | Artículo publishedVersion |
| Lenguaje: | Inglés |
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2004
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_15253961_v5_n3_p261_GomezCasati |
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paperaa:paper_15253961_v5_n3_p261_GomezCasati2023-06-12T16:50:36Z Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells JARO J. Assoc. Res. Otolaryngol. 2004;5(3):261-269 Gomez-Casati, M.E. Katz, E. Glowatzki, E. Lioudyno, M.I. Fuchs, P. Elgoyhen, A.B. 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 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. Fil:Gomez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2004 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15253961_v5_n3_p261_GomezCasati |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Gomez-Casati, M.E. Katz, E. Glowatzki, E. Lioudyno, M.I. Fuchs, P. Elgoyhen, A.B. |
| author_facet |
Gomez-Casati, M.E. Katz, E. Glowatzki, E. Lioudyno, M.I. Fuchs, P. Elgoyhen, A.B. |
| author_sort |
Gomez-Casati, M.E. |
| title |
Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells |
| title_short |
Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells |
| title_full |
Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells |
| title_fullStr |
Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells |
| title_full_unstemmed |
Linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells |
| title_sort |
linopirdine blocks α9α10-containing nicotinic cholinergic receptors of cochlear hair cells |
| publishDate |
2004 |
| url |
http://hdl.handle.net/20.500.12110/paper_15253961_v5_n3_p261_GomezCasati |
| work_keys_str_mv |
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| _version_ |
1769810298606190592 |