Inhibition of gap junctional coupling in cochlear supporting cells by gentamicin.
Gap junctional coupling of cochlear supporting cells is thought to be responsible for spatial potassium buffering of the microenvironment of outer hair cells (OHC). OHC of the organ of Corti are considered as the target of aminoglycoside-induced ototoxicity. Due to the proposed functional relationship between OHC and cochlear supporting cells we investigated a possible involvement of the supporting Hensen cells in the ototoxic effect of the aminoglycoside gentamicin. Isolated Hensen cell pairs were superfused by gentamicin-containing bath solutions. Using the double whole-cell patch-clamp method gentamicin (10 microM) inhibited gap junctional conductance by about 90%, whereas the membrane potential of about -27 mV remained unchanged. Since the inhibitory effect was suppressed by the addition of catalase, the gentamicin mediated effect probably is due to production of free radicals. It is proposed that formation of free radicals in supporting cells inhibits gap junctional coupling whereby the spatial potassium buffer mechanism and, thus, the fine tuning of the cochlear OHC is impaired.
Todt
I
I
Institute of Biophysics, University of Hannover, Germany.
Ngezahayo
A
A
Ernst
A
A
Kolb
H A
HA
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004553:Electric Conductivity; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology*; D005839:Gentamicins / Q000494:pharmacology*; D006168:Guinea Pigs; D018408:Patch-Clamp Techniques
D004338:Drug Combinations; D005839:Gentamicins; D002374:Catalase