title: Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus.
abstract: Vulnerability to noise-induced tinnitus is associated with increased spontaneous firing rate in dorsal cochlear nucleus principal neurons, fusiform cells. This hyperactivity is caused, at least in part, by decreased Kv7.2/3 (KCNQ2/3) potassium currents. However, the biophysical mechanisms underlying resilience to tinnitus, which is observed in noise-exposed mice that do not develop tinnitus (non-tinnitus mice), remain unknown. Our results show that noise exposure induces, on average, a reduction in KCNQ2/3 channel activity in fusiform cells in noise-exposed mice by 4 days after exposure. Tinnitus is developed in mice that do not compensate for this reduction within the next 3 days. Resilience to tinnitus is developed in mice that show a re-emergence of KCNQ2/3 channel activity and a reduction in HCN channel activity. Our results highlight KCNQ2/3 and HCN channels as potential targets for designing novel therapeutics that may promote resilience to tinnitus.
authors: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors: Shuang
authors: S
authors: Li
authors: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors: Bopanna I
authors: BI
authors: Kalappa
authors: Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors: Thanos
authors: T
authors: Tzounopoulos
mesh_terms: D000818:Animals; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009622:Noise; D014012:Tinnitus / Q000503:physiopathology*
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C114401:Kcnq2 protein, mouse; C496917:Kcnq3 protein, mouse; D009419:Nerve Tissue Proteins
keywords: HCN channels; homeostatic plasticity; hyperexcitability-related disorders; mouse; neuroscience; potassium channels; tinnitus