Potassium voltage-gated channel subfamily KQT member 4 (Kv7.4) (Kv7.4)

Potassium voltage-gated channel subfamily KQT member 4 (Kv7.4) is a transmembrane protein encoded by the KCNQ4 gene that functions as a voltage-dependent potassium channel. It is predominantly expressed in the outer hair cells of the cochlea and the vestibular system, where it plays a critical role in recycling potassium ions and maintaining the electrical properties necessary for auditory transduction (UniProt O43526). Mutations in this channel are the primary cause of DFNA2, a form of progressive, nonsyndromic sensorineural hearing loss (Kubisch et al., 1999, PMID: 10072428). In addition to its role in the ear, Kv7.4 is expressed in vascular smooth muscle and certain brainstem neurons, influencing vascular resistance and central auditory processing (Jepps et al., 2011, PMID: 21670110). Therapeutic interest in Kv7.4 focuses on the development of selective activators to treat hearing loss and tinnitus by stabilizing the membrane potential of hair cells. However, achieving selectivity is challenging due to the high structural homology between Kv7.4 and other members of the KCNQ family, which can lead to cardiovascular or neurological side effects (Gunthorpe et al., 2012, PMID: 22407153).

Other names

KCNQ4Potassium channel subunit alpha Kv7.4DFNA2DFNA2AVoltage-gated potassium channel subunit Kv7.4

Positive allosteric modulation to increase channel opening probability or shift voltage-dependence of activation; pore blockade for inhibition.