Target intelligence / Profile preview

Potassium channel subfamily T member 1 (KCNT1)

Target
KCNT1
Molecular classification
Ion channel, Potassium channel, Sodium-activated potassium channel
01

Overview

Potassium channel subfamily T member 1 (KCNT1) is a sodium-activated potassium channel protein chiefly expressed in the brain, where it regulates neuronal excitability by controlling potassium ion efflux during action potentials. The channel comprises four alpha subunits and is critical for the development and function of neuronal circuits. Gain-of-function mutations lead to increased channel activity and are implicated in a spectrum of pharmacoresistant epileptic encephalopathies, including malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. The channel is also known as SLACK or KCa4.1, and therapeutic research targets both its abnormal function and gene expression.

Other names
KCa4.1KIAA1422Slo2.2SLACKKNa1.1potassium channel, sodium activated subfamily T, member 1potassium sodium-activated channel subfamily T member 1
02

Mechanism of action

Channel blockers (e.g., tetraethylammonium) inhibit potassium efflux, modulating neuronal excitability - Channel activators (e.g., phorbol 12-myristate 13-acetate) enhance potassium channel activity, potentially affecting neuronal burst firing

03

Biological functions

Regulates neuronal excitabilityModulates potassium ion currents during repolarizationGoverns action potential firing in neuronsContributes to synaptic development and plasticityInvolved in signal transduction in neurons
04

Disease associations

Epileptic encephalopathyDevelopmental and epileptic encephalopathyMalignant migrating partial seizures of infancyAutosomal dominant nocturnal frontal lobe epilepsyOhtahara syndromeOther severe early-onset epilepsy syndromes
05

Safety considerations

Severe developmental delay and neurological impairment in patients with pathogenic variantsPharmacoresistance (poor response to anticonvulsants)Sudden unexpected death in epilepsy (SUDEP)
06

Interacting drugs

Tetraethylammonium (blocker)

1 more in the full profile.

07

Biomarkers

KCNT1 pathogenic gene variants for diagnosis and patient selection in epilepsy syndromes

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