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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 27, 2015
- Source ID
- 10.7554/elife.07242
Entities
People
- Bopanna I Kalappa
- Shuang Li
- Thanos Tzounopoulos
Organizations
- National Institute on Deafness and Other Communication Disorders
- United States Department of Defense
- University of Pittsburgh