Potassium voltage-gated channel subfamily KQT member 3 (KCNQ3) (KCNQ3)

Potassium voltage-gated channel subfamily KQT member 3 (KCNQ3), also known as Kv7.3, is a transmembrane protein that forms voltage-activated potassium channels primarily in the brain (UniProt: Q9Y271). While KCNQ3 is most recognized for forming heteromeric channels with KCNQ2 to generate the M-current, it can also form functional homomeric channels that contribute to the regulation of neuronal excitability (PubMed: 10531319). These homomeric channels are characterized by a low conductance but play a role in stabilizing the resting membrane potential and controlling the frequency of action potential firing (PubMed: 15548531). Mutations in the KCNQ3 gene are a known cause of Benign Familial Neonatal Seizures (BFNS), an autosomal dominant epilepsy syndrome (NCBI Gene: 3786). Pharmacological agents like retigabine (ezogabine) act as positive allosteric modulators of KCNQ3-containing channels, facilitating their opening at more negative voltages to reduce neuronal hyperexcitability (PubMed: 21339371). Consequently, KCNQ3 is a significant therapeutic target for epilepsy, neuropathic pain, and potentially mood disorders (PubMed: 25163914). However, targeting these channels presents challenges, such as the risk of urinary retention and pigmentary changes associated with non-selective Kv7 openers (FDA: Ezogabine Safety Communication). Research continues into subtype-selective modulators that might offer better safety profiles by specifically targeting KCNQ3 or its heteromers over other Kv7 family members (PubMed: 29632134).

Other names

Kv7.3Potassium channel subunit KQT3KQT-like 3BFNC2KCNQ3 homomeric channel

Positive allosteric modulation (opening) of the channel to enhance potassium efflux and hyperpolarize the neuronal membrane.