Zusammenfassung
Hintergrund: Therapeutische Dosen von Chinin (wie auch von Salicylaten) können eine reversible Hörminderung und Ohrgeräusche verursachen. Die Ergebnisse von Ableitungen unterschiedlicher akustisch evozierter Potenziale ließen darauf schließen, dass die kochleären äußeren Haarzellen den Hauptangriffsort für die ototoxischen Wirkungen dieser Substanz darstellen.
Methode: Isolierte äußere Haarzellen der Meerschweinchenkochlea wurden in primärer Zellkultur mit ototoxischen Konzentrationen von Chininhydrochlorid (50 µmol/l bis 1,5 mmol/l) umspült. Mit Patch-clamp-Techniken in Ganz-Zell-Konfiguration erfolgte die Stimulation der Haarzellen zur Analyse der Elektromotilität und der Membranpotenziale. Zur Darstellung der Feinstruktur nach Chininapplikation wurden isolierte Haarzellen fixiert und transmissionselektronenmikroskopisch untersucht.
Ergebnisse: Nach Chininexposition zeigten die äußeren Haarzellen eine initiale Hyperpolarisation des Membranpotenzials, gefolgt von einer Depolarisation. Meistens ließ sich eine Verminderung der Elektromotilität beobachten, die sich nach hyperpolarisierenden Spannungspulsen deutlicher ausprägte als nach Depolarisation. Diese Effekte waren nach Spülung mit chininfreier artifizieller Perilymphlösung reversibel. Licht- oder elektronenmikroskopisch waren keine strukturellen Veränderungen, die direkt auf Chinineinfluss zurückzuführen wären, darstellbar.
Schlussfolgerungen: Chinin führt zu einer direkten und reversiblen Veränderungen an den kochleären äußeren Haarzellen und damit direkt am kochleären Verstärkermechanismus. Im Gegensatz zu Salicylaten beeinflusst Chinin jedoch nicht den Turgor oder die Feinstruktur der äußeren Haarzellen. Trotz identischer ototoxischer Symptome von Chinin und Salicylaten scheint somit der Wirkmechanismus beider Substanzen grundlegend unterschiedlich zu sein.
Abstract
Background: Large doses of quinine (as well as of salicylate) are known to produce reversible hearing loss and tinnitus. Cochlear outer hair cells seem to be the common site for the ototoxic effect of both drugs.
Methods: Isolated outer hair cells from the guinea pig cochlea were exposed to ototoxic doses of quinine hydrochloride (0.05-1.5 mmol/l). The cells were examined using tight-seal whole-cell recording techniques and transmission electron microscopy.
Results: Quinine exposure led to a hyperpolarization followed by a depolarization of the hair cells’ membrane potential. It also caused a diminution of evoked rapid motile responses that was more apparent in response to hyperpolarizing than to depolarizing pulses. These effects were largely dose dependent and reversible. Ototoxic doses of quinine were not found to induce changes in turgor, shape or fine structure of outer hair cells such as those reported with ototoxic doses of salicylates in vitro.
Conclusions: The present in vitro findings show that quinine (as well as salicylate) directly and reversibly affects cochlear outer hair cells. They also indicate that the underlying mechanisms of quinine ototoxicity are considerably different to that of salicylate although both substances clinically lead to identical symptoms.
Schlüsselwörter
Meerschweinchen - Kochlea - Isolierte äußere Haarzellen - Chinin - Elektromotilität - Feinstruktur
Key words
Guinea pig - Cochlea - Isolated outer hair cells - Electromotility - Quinine - Fine structure
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Priv.-Doz. Dr. med. Ralf Dieler
Bayerische Julius-Maximilians-Universität · Klinik und Poliklinik für Hals-, Nasen- und Ohrenkranke
Josef-Schneider-Str. 11 · 97080 Würzburg ·
eMail: r.dieler@mail.uni-wuerzburg.de