A potassium channel agonist protects hearing function and promotes outer hair cell survival for age-related hearing loss

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Abstract​

Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function.

A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss - Cell Death & Disease

Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated...

nature.com

KCNQ4 Activators​

• Retigabine
• Zinc Pyrithione
• Maxipost
• Acrylamide

Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss

Potassium voltage-gated channel subfamily q member 4 (KCNQ4) is a voltage-gated potassium channel that plays essential roles in maintaining ion homeostasis and regulating hair cell membrane potential. Reduction of the activity of the KCNQ4 channel owing ...

ncbi.nlm.nih.gov

Intracellular zinc and ascorbate potentiate KCNQ4 channel.

Intracellular Zinc and Ascorbate Potentiate KCNQ Currents via Distinct Mechanisms

KCNQ (Kv7) potassium voltage-gated channels are expressed in the dorsal root ganglion (DRG) sensory neurons where they play an important role in controlling DRG neuron excitability. Therefore, any substance modulating the activity of these channels could significantly affect the thresholds and...

www.cell.com

Zinc ionophores are KCNQ channel openers.

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate

M-type (Kv7, KCNQ) potassium channels are powerful regulators of neuronal and muscular excitability and are validated drug targets for the treatment of excitability disorders. The plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate ...

ncbi.nlm.nih.gov

Vardenafil, a PDE5 inhibitor, prevent the loss of surface KCNQ4 from outer hair cells induced by acoustic trauma.

cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function - PubMed

Noise-induced hearing loss (NIHL) is a global health hazard with considerable pathophysiological and social consequences that has no effective treatment. In the heart, lung and other organs, cyclic guanosine monophosphate (cGMP) facilitates protective processes in response to traumatic events...

ncbi.nlm.nih.gov

Minoxidil is also a potassium channel opener, but its effect on KCNQ4 channel is unknown. Maybe the treatment of hair loss on the head and hair loss inside the ear is the same!