Potassium voltage-gated channel subfamily C member 4 and member 2 (Kv3.4/Kv3.2)

Kv3.4 and Kv3.2 are members of the Shaw-related (Kv3) subfamily of voltage-gated potassium channels, characterized by high activation thresholds and exceptionally rapid activation and deactivation kinetics [4, 8, 13]. These properties allow specific neurons, such as fast-spiking interneurons and auditory neurons, to fire action potentials at very high frequencies by ensuring rapid repolarization without increasing the refractory period [8, 13, 31]. While Kv3.2 typically forms delayed rectifier channels, Kv3.4 contributes a fast-inactivating (A-type) component, and their heteromerization fine-tunes the firing properties of central nervous system circuits [10, 13, 15]. Dysregulation of these channels is implicated in several neurological and psychiatric conditions, including Alzheimer's disease, where Kv3.4 is often overexpressed and associated with amyloid-beta toxicity, and schizophrenia, where Kv3.2 dysfunction may disrupt gamma oscillations [18, 25, 26, 33, 34]. Pharmacological targeting of these channels, particularly with positive allosteric modulators like the AUT series, is being explored to restore inhibitory balance in the brain and treat cognitive deficits [31, 32, 33, 37]. However, the widespread expression of Kv3 channels in the brain necessitates careful selectivity to avoid adverse effects such as seizures or motor dysfunction [2, 4, 31].

Other names

KCNC4KCNC2Kv3.4Kv3.2Potassium voltage-gated channel subfamily C member 4Potassium voltage-gated channel subfamily C member 2Shaw-related subfamily C member 4Shaw-related subfamily C member 2A-type potassium channel (Kv3.4)Delayed rectifier potassium channel (Kv3.2)MiRP2-Kv3.4 complex

Positive allosteric modulation of channel opening or blockade of the ion-conducting pore to regulate neuronal excitability and firing frequency.