Changes in transient receptor potential cation channel superfamily V (TRPV) mRNA expression in the mouse inner ear ganglia after kanamycin challenge.
The transient receptor potential cation channel subfamily V (TRPV) is a non-specific cation ion channel receptor family that is gated by heat, protons, low extracellular osmolarity and arachidonic acid derivatives. Since some of these endogenous agonists of TRPV receptors are reactive oxygen intermediates produced by lipoxygenases, it has been hypothesized that some members of the TRPV family may respond to challenges by reactive oxygen species. This study used real-time PCR to quantitatively track changes in TRPV1-4 mRNA expression in the spiral, vestibular, and trigeminal ganglia and the kidney from kanamycin (KM)-treated mice. TRPV1, TRPV2, TRPV3 and TRPV4 mRNAs were expressed in spiral and vestibular ganglia, and TRPV2 and TRPV1 mRNAs were most predominant in control mice. After KM (700 mg/kg s.c. b.i.d., 14 days), TRPV1 mRNA and protein expression were significantly up-regulated both in the spiral and vestibular ganglia, but expression was unaffected in the trigeminal ganglion and kidney. Real-time PCR also demonstrated a significant down-regulation in TRPV4 mRNA expression in the inner ear ganglia and kidney after KM treatment. All these mRNA and protein expression changes were eliminated by simultaneous administration of dihydroxybenzoate (300 mg/kg s.c. b.i.d., 14 days), an anti-oxidant that blocks KM ototoxicity. It is proposed that up-regulated TRPV1 expression during KM exposure may promote ganglion cell survival by contributing to neuronal depolarization, with KM-induced tinnitus and dizziness as consequences.
Kitahara
Tadashi
T
Department of Otolaryngology, University of Pittsburgh School of Medicine, 107 Eye and Ear Institute, Room 153, 203 Lothrop Street, Pittsburgh, PA 15213, USA.
Li
Ha-Sheng
HS
Balaban
Carey D
CD
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D015153:Blotting, Western; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D007758:Ear, Inner / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D007612:Kanamycin / Q000009:adverse effects / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016133:Polymerase Chain Reaction; D012107:Research Design; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D050916:TRPV Cation Channels; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014725:Vestibular Nerve / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D007612:Kanamycin