KCNT1 Antibodies

Structure of KCNT1

KCNT1 is a large transmembrane protein with a molecular weight of approximately 130-140 kDa. Its precise molecular weight varies among different species due to splicing variants.

This protein is composed of approximately 1,200 amino acids, and its primary structure folds into a typical pore protein conformation containing six transmembrane segments (S1-S6). The uniqueness of KCNT1 lies in the fact that its cytoplasmic C-terminal contains a distinctive regulatory domain (RCK2). This domain regulates the opening of channels by sensing the concentrations of sodium ions and ATP within the cell, thereby precisely controlling the effervescence of potassium ions. The selective filter formed by its pore loop region ensures the efficient passage of potassium ions, while the S4 transmembrane segment serves as a voltage sensor, making the channel sensitive to changes in membrane potential.

Fig. 1 Distribution of the studied mutations on the 3D model of the KCNT1 channel.¹

Key structural properties of KCNT1:

• Typical pore architecture consisting of six transmembrane domains (S1-S6)
• Unique intracellular RCK2 structure domain is responsible for sodium ions combine with ATP
• The P-loop forms a potassium ion-selective filter

Functions of KCNT1

The core function of the protein encoded by the KCNT1 gene is to regulate neuronal excitability, and its mutations are closely related to various neurological diseases.

The current-voltage relationship of this channel presents an inward rectification characteristic, and its activation process is simultaneously regulated by both membrane potential and intracellular sodium ion concentration. This characteristic is crucial for understanding its pathophysiological mechanism in epilepsy.

Applications of KCNT1 and KCNT1 Antibody in Literature

1. Di Matteo, Francesca, et al. "KCNT1 Channel Blockers: A Medicinal Chemistry Perspective." Molecules 29.12 (2024): 2940. https://doi.org/10.3390/molecules29122940

The article indicates that the KCNT1 potassium channel has become an important target for the treatment of epilepsy. At present, the development of blockers for this channel is still in its early stage. This paper systematically reviews the chemical structures and screening methods of the discovered KCNT1 blockers, and analyzes the advantages and disadvantages of various research strategies.

2. Burbano, Lisseth Estefania, et al. "Antisense oligonucleotide therapy for KCNT1 encephalopathy." JCI insight 7.23 (2022): e146090. https://doi.org/10.1172/jci.insight.146090

This study developed a precise gene silencing therapy for developmental epileptic encephalopathy caused by KCNT1 gene mutations. By injecting KCNT1-targeted antisense oligonucleotides (ASO) into diseased mouse models, epileptic seizures were effectively controlled, behavioral abnormalities were improved, and survival periods were significantly prolonged, providing a new proof of concept for the treatment of KCNT1-related epilepsy.

3. Shore, Amy N., et al. "Heterozygous expression of a Kcnt1 gain-of-function variant has differential effects on somatostatin-and parvalbumin-expressing cortical GABAergic neurons." Elife 13 (2024): RP92915. https://doi.org/10.7554/eLife.92915

This study aimed to reveal the pathogenic mechanism of the KCNT1 functional gain mutation and found that this mutation had opposite effects on two types of inhibitory neurons, SST and PV, in the mouse cortex: the excitability of the former decreased, while that of the latter increased. This difference stems from the interaction with different ion channels, providing new cellular targets for precision treatment.

4. Rychkov, Grigori Y., et al. "Functional effects of epilepsy associated KCNT1 mutations suggest pathogenesis via aberrant inhibitory neuronal activity." International journal of molecular sciences 23.23 (2022): 15133. https://doi.org/10.3390/ijms232315133

This study systematically analyzed the functional effects of various KCNT1 mutations and found that most mutations would enhance channel current or the probability of opening, and the degree of change was positively correlated with the severity of neurological diseases. The results indicated that the gain-of-function mutation of KCNT1 might eventually lead to epileptic seizures by increasing resting potassium conductivity and inhibiting inhibitory neuronal activity.

5. Kim, Grace E., and Leonard K. Kaczmarek. "Emerging role of the KCNT1 Slack channel in intellectual disability." Frontiers in cellular neuroscience 8 (2014): 209. https://doi.org/10.3389/fncel.2014.00209

The article indicates that the potassium channel KCNT1 (Slack) is a key regulator of neuronal excitability. Abnormal function of this channel is associated with intellectual disability and childhood epilepsy. The mechanism involves interaction with fragile X mental retardation protein (FMRP) and affects delayed outward potassium current, making it an important target for neurological disease research.

Creative Biolabs: KCNT1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality KCNT1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom KCNT1 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our KCNT1 antibodies, custom preparations, or technical support, contact us at email.