Potassium voltage-gated channel subfamily C member 1 and 2 (Kv3.1/Kv3.2)

Kv3.1 and Kv3.2 are voltage-gated potassium channels encoded by the KCNC1 and KCNC2 genes, respectively, belonging to the Shaw-related (Kv3) subfamily [1, 5]. They are uniquely characterized by high activation thresholds and exceptionally fast activation and deactivation kinetics, which are essential for the rapid repolarization of action potentials [1, 16]. This allows specific neuronal populations, such as parvalbumin-positive GABAergic interneurons and auditory brainstem neurons, to sustain high-frequency firing rates up to 1000 Hz [1, 14]. In the central nervous system, these channels play a pivotal role in regulating neuronal excitability and synchronizing network activity, including the generation of gamma oscillations [8, 12]. Mutations or reduced expression of Kv3.1/3.2 are associated with a range of neurological and psychiatric conditions, including progressive myoclonus epilepsy, schizophrenia, and age-related hearing loss [1, 6, 13]. Pharmacological targeting of these channels primarily involves positive allosteric modulators (PAMs), such as AUT00206 and AUT00063, which aim to restore the firing capacity of inhibitory interneurons and correct excitatory-inhibitory imbalances [2, 8, 20].

Other names

KCNC1KCNC2NGK2Shaw-related subfamily C member 1Shaw-related subfamily C member 2Voltage-gated potassium channel subunit Kv3.1Voltage-gated potassium channel subunit Kv3.2

Positive allosteric modulation (PAM) of Kv3.1 and Kv3.2 channels, which shifts the voltage-dependence of activation to more negative potentials and increases the firing frequency of fast-spiking neurons.