KCNQ2/3 and HCN Channels Underlies Vulnerability and Resilience to Tinnitus

[Danny Boy]

Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus

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.

 

[Lucifer]

@Nick47, @StoneInFocus, I know this is an old thread but I wanted to get your opinion on what you reckon is causing hyperacusis/noxacusis; Kv potassium channels or HCN channels.

I saw you were discussing the Prof. McNaughton study on using Ivabradine to open HCN2 channels in Guinea Pigs with success.

Two Kv potassium channel drugs are currently in clinical trials: BHV-7000 and XEN1101, with XEN1101 in their Phase 3 trial and with BHV-7000 starting their Phase 2/3 pivotal phase trial later this year.

Other than Ivabradine and Merck2, which is still in preclinical, are there any other HCN drugs in clinical trials or any natural remedies that can target HCN2?

 

[Nick47]

@Nick47, @StoneInFocus, I know this is an old thread but I wanted to get your opinion on what you reckon is causing hyperacusis/noxacusis; Kv potassium channels or HCN channels.

I saw you were discussing the Prof. McNaughton study on using Ivabradine to open HCN2 channels in Guinea Pigs with success.

Two Kv potassium channel drugs are currently in clinical trials: BHV-7000 and XEN1101, with XEN1101 in their Phase 3 trial and with BHV-7000 starting their Phase 2/3 pivotal phase trial later this year.

Other than Ivabradine and Merck2, which is still in preclinical, are there any other HCN drugs in clinical trials or any natural remedies that can target HCN2?

Both seem to be the answer as these ion channels in the cell membrane change the action potentials of the cells.

I'm not aware of any other candidates around.

This is a slightly more recent summary. It mentions the importance of selectivity in HCN channel blockers:

Oxford Talks: HCN2 ion channels – drivers of chronic pain and tinnitus