Potassium voltage-gated channel subfamily Q member 2 - M-channel subunit regulating neuronal excitability
KCNQ2 (Kv7.2) is a voltage-gated potassium channel subunit important for neuronal excitability. [1]
| Gene | [KCNQ2](/genes/kcnq2) |
| UniProt | [UniProt:O43526](https://www.uniprot.org/uniprot/O43526) |
| PDB IDs | [PDB:6UUM](https://www.rcsb.org/structure/6UUM), [PDB:6UUN](https://www.rcsb.org/structure/6UUN), [PDB:5V4Z](https://www.rcsb.org/structure/5V4Z) |
| Molecular Weight | 95 kDa |
| Localization | Plasma membrane |
| Protein Family | Voltage-gated potassium channel, Kv7 family |
KCNQ2 contains six transmembrane segments (S1-S6), with S4 serving as the voltage sensor. The pore region is located between S5 and S6. The N-terminus contains a subunit interaction domain (A-domain) that mediates assembly with KCNQ3. The C-terminus contains a calmodulin binding domain that regulates channel trafficking and activity.
KCNQ2 is phosphorylated by multiple kinases including PKA and PKC, which modulate channel trafficking and activity. Ubiquitination regulates channel degradation.
KCNQ2 (Kv7.2) is a voltage-gated potassium channel that generates the M-current, a slowly activating and non-inactivating potassium current critical for regulating neuronal excitability [1]. KCNQ2 forms homomeric or heteromeric channels with KCNQ3 to produce the M-channel, which dampens neuronal firing and prevents hyperexcitability. These channels are heavily expressed in hippocampal neurons, cortical pyramidal cells, and motoneurons. The M-current is a key target for neuromodulators and plays essential roles in learning, memory, and seizure suppression.
KCNQ2 mutations cause benign familial neonatal seizures (BFNS) and early-onset epileptic encephalopathies including Ohtahara syndrome and West syndrome [2]. Over 200 pathogenic mutations have been identified, including loss-of-function mutations that reduce M-current amplitude and gain-of-function mutations that cause hyperexcitability. KCNQ2 encephalopathy presents with severe seizures, developmental delay, and characteristic EEG patterns. KCNQ2 dysfunction also contributes to neuronal hyperexcitability in Alzheimer's disease and may represent a therapeutic target [3].
Retigabine (ezogabine) is a KCNQ2/3 channel opener approved for epilepsy that enhances M-current and reduces neuronal hyperexcitability [4]. Novel KCNQ2/3 activators including ICA-69673 and SF0034 are in development with improved pharmacological profiles. Antisense oligonucleotides targeting pathogenic KCNQ2 variants are being explored for genetic epilepsies.
Weckhuysen et al. KCNQ2 encephalopathy (2016). 2016. ↩︎