Effects of local anaesthetics on the gross receptor potentials in the guinea pig cochlea. 1997

W Jäger, and L Brundin, and E Idrizbegovic, and A Flock
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Local anaesthetics have been used intravenously and intratympanally to reduce tinnitus. In order to clarify its action in the periphery, we applied 0.5 mM tetracaine in the scala tympani in 18 cochleae and studied the effects on the receptor potentials. We used a temporal bone preparation of the guinea pig ear in vitro exposing the fourth cochlear turn where the cochlear microphonics (CM) and the summating potential (SP) were recorded. The perfusion was kept at a rate of 50 microliters/min. The frequency response of the cochlea was determined at the beginning of each experiment and the responses were recorded at the best frequency of the preparation. In another five cochleae an accumulated dose-response relationship was determined by increasing the tetracaine concentration in steps (50, 100, 300, 500, 1000 and 2000 microM), measuring the difference in amplitude of the receptor potentials. The CM decreased significantly (p < 0.001; mean 0.37 mV; SD 0.29). In 12 cochleae the SP was initially positive and did not increase significantly (p = 0.16; mean 0.07 mV; SD 0.16). In six cochleae the SP was initially negative and all changed polarity to positive and increased significantly (p < 0.05; mean 0.36 mV; SD 0.28). The effects on both the CM and the SP were reversible. Owing to the inter-individual variation between the cochleae the SP/CM ratio was determined and it increased significantly (p < 0.001; mean 0.18; SD 0.11). In the accumulated dose-response experiments the CM decreased significantly (p < 0.05) in a dose-dependent way, whereas the SP did not increase significantly. The SP/CM ratio increased significantly (p < 0.05) at 300 microM and 500 microM. We hypothesize that the peripheral tinnitus-reducing action of local anaesthetics is in part due to a reversal of the SP, but also to a reduction of the CM. The difference in effect of tetracaine on the receptor potentials, the CM and the SP, suggests that the SP is not dependent on the CM.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D003051 Cochlea The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH. Cochleas
D003055 Cochlear Microphonic Potentials The electric response of the cochlear hair cells to acoustic stimulation. Cochlear Microphonic Potential,Potential, Cochlear Microphonic,Potentials, Cochlear Microphonic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000779 Anesthetics, Local Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate. Anesthetics, Conduction-Blocking,Conduction-Blocking Anesthetics,Local Anesthetic,Anesthetics, Topical,Anesthetic, Local,Anesthetics, Conduction Blocking,Conduction Blocking Anesthetics,Local Anesthetics,Topical Anesthetics
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012533 Scala Tympani The lower chamber of the COCHLEA, extending from the round window to the helicotrema (the opening at the apex that connects the PERILYMPH-filled spaces of scala tympani and SCALA VESTIBULI). Scala Tympanus,Tympani, Scala,Tympanus, Scala
D013748 Tetracaine A potent local anesthetic of the ester type used for surface and spinal anesthesia. Tetrakain,Amethocaine,Ametop,Dicaine,Pantocaine,Pontocaine,Tetracaine Monohydrochloride,Tetrracaine Hydrochloride,Hydrochloride, Tetrracaine

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