Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice.
Ion channels in the degenerin-epithelial sodium channel (DEG-ENaC) family perform diverse functions, including mechanosensation. Here we explored the role of the vertebrate DEG-ENaC protein, acid-sensing ion channel 2 (ASIC2), in auditory transduction. Contributions of ASIC2 to hearing were examined by comparing hearing threshold and noise sensitivity of wild-type and ASIC2 null mice. ASIC2 null mice showed no significant hearing loss, indicating that the ASIC2 was not directly involved in the mechanotransduction of the mammalian cochlea. However, we found that (1) ASIC2 was present in the spiral ganglion (SG) neurons in the adult cochlea and that externally applied protons induced amiloride-sensitive sodium currents and action potentials in SG neurons in vitro, (2) proton-induced responses were greatly reduced in SG neurons obtained from ASIC2 null mice, indicating that activations of ASIC2 contributed a major portion of the proton-induced excitatory response in SG neurons, and (3) ASIC2 null mice were considerably more resistant to noise-induced temporary, but not permanent, threshold shifts. Together, these data suggest that ASIC2 contributes to suprathreshold functions of the cochlea. The presence of ASIC2 in SG neurons could provide sensors to directly convert local acidosis to excitatory responses, therefore offering a cellular mechanism linking hearing losses caused by many enigmatic causes (e.g., ischemia or inflammation of the inner ear) to excitotoxicity.
Peng
Ben-Gang
BG
Section on Neurobiology, Gonda Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, California 90057, USA.
Ahmad
Shoab
S
Chen
Shanping
S
Chen
Ping
P
Price
Margaret P
MP
Lin
Xi
X
D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001309:Auditory Threshold; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D002794:Choline / Q000494:pharmacology; D003051:Cochlea / Q000503:physiopathology*; D004546:Elapid Venoms / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry; D006309:Hearing / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009622:Noise / Q000009:adverse effects*; D018408:Patch-Clamp Techniques; D011522:Protons; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D004546:Elapid Venoms; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D015222:Sodium Channels; C020273:dendrotoxin; D000584:Amiloride; D002794:Choline