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

Potassium voltage-gated channel subfamily C member 1 (Kv3.1) is a transmembrane protein encoded by the KCNC1 gene that forms voltage-gated potassium channels essential for high-frequency neuronal firing [UniProt: P48547]. It is characterized by a high activation threshold and very rapid deactivation kinetics, allowing neurons to fire at rates exceeding 100 Hz by quickly repolarizing the action potential without increasing the refractory period [PubMed: 25849173]. Kv3.1 is predominantly expressed in the central nervous system, particularly in fast-spiking parvalbumin-positive interneurons and auditory brainstem neurons [NCBI Gene: 3746]. Mutations in the KCNC1 gene are linked to progressive myoclonus epilepsy (EPM7) and other neurodevelopmental disorders, emphasizing its role in maintaining neural circuit stability [PubMed: 25401298]. Therapeutic interest in Kv3.1 focuses on positive allosteric modulators (PAMs) to treat conditions like schizophrenia and hearing loss by restoring normal firing patterns [ClinicalTrials.gov: NCT02315508]. Compounds such as AUT00063 and AUT00206 have been explored in clinical trials for these indications, aiming to enhance channel activity in specific neuronal populations. However, achieving selectivity over other Kv3 family members remains a significant therapeutic challenge to avoid unwanted neurological side effects.

Other names

KCNC1Voltage-gated potassium channel subunit Kv3.1Shaw-related subfamily member 1NGK2KV3.1

Positive allosteric modulation (PAM) to enhance channel opening kinetics and facilitate high-frequency neuronal firing [PubMed: 25849173].