Tetraethylammonium ions block the nicotinic cholinergic receptors of cochlear outer hair cells.
Cochlear outer hair cells (OHCs) express nicotinic acetylcholine receptors (nAChRs) whose calcium permeability allow the activation of co-localized Ca(2+)-sensitive K+ channels (SK-type). The large organic cation tetraethylammonium (TEA) is known to block at millimolar concentration voltage-gated and Ca(2+)-activated K+ currents in OHCs. In the present study, we show that extracellular TEA blocked much more efficiently, at micromolar concentrations, ACh-evoked K+ currents in isolated guinea pig OHCs. The dose-inhibition curve indicated an IC(50) of 60 microM, a value two orders of magnitude lower than the one reported on SK or BK channels. The site of the blocking action was on the extracellular side of the plasma membrane since 10 mM intracellular TEA did not prevent or change the characteristics of the ACh-evoked K+ current. The block of this K+ current in OHCs was mainly explained by a direct action of TEA at the nAChRs. Indeed, we demonstrated that extracellular TEA inhibited directly the ionotropic cation current flowing through the nAChRs (IC(50)=30 microM). This study demonstrated for the first time that extracellular TEA is an effective blocker of the OHCs' nAChRs.
Blanchet
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Laboratoire de Biologie Cellulaire et Moléculaire de l'Audition, Equipe Mixte INSERM 99-27, Université de Bordeaux 2, CHU Hôpital Pellegrin, 33076 Bordeaux, France.
Dulon
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D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006309:Hearing / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011978:Receptors, Nicotinic; D019789:Tetraethylammonium; D000109:Acetylcholine