Voltage-gated potassium channel subfamily K member 2 (Kv7.2)

Kv7.2 is a voltage-gated potassium channel encoded by the KCNQ2 gene and is a key member of the Kv7 family. It functions as a tetramer of alpha subunits, which can be homomeric Kv7.2 or heteromeric, most notably with Kv7.3 subunits, to form the neuronal M-current. Each subunit has six transmembrane segments (S1-S6), cytoplasmic N- and C-termini. The S1-S4 segments form the voltage-sensing domain, while S5-S6 and the linker form the pore domain. A distinctive long C-terminus contains domains for tetramerization and binding sites for regulatory molecules like PIP2, calmodulin, syntaxin, etc. Kv7.2 channels generate voltage-activated, slowly activating, and non-inactivating potassium currents that open at subthreshold membrane potentials (around -60 mV). This current is essential for controlling neuronal excitability by setting the resting potential, determining spike threshold and firing frequency, preventing hyperexcitability, and mediating after-hyperpolarization. Channel activity is regulated by voltage, calcium-bound and unbound calmodulin, PIP2, and various signaling cascades. Mutations in the KCNQ2 gene leading to Kv7.2 dysfunction are associated with neuronal hyperexcitability and several neurological disorders, particularly epilepsy, making Kv7.2 an important therapeutic target. Pharmacologically, Kv7.2 channels can be modulated by drugs like the activators Retigabine and flupirtine, which shift the voltage-dependence of activation and are used to treat conditions involving neuronal hyperexcitability.

Other names

KCNQ2

Modulating neuronal excitability by increasing or decreasing the activity of Kv7.2 channels, often by shifting the voltage-dependence of channel activation.