GaTx2

Product Name:GaTx2

CAS No:194665-85-5

Purity:95%

Molar Mass:3192.54

Chemical Formula:C125H199N39O47S6

Storage:Store at -20 degrees Celsius

Sequence:VSCEDCPDHCSTQKARAKCDNDKCVCEPI

Target:ClC-2 channel

Application:

GaTx2 is a peptide that acts as a blocker of the ClC-2 chloride channels. ClC-2 channels are involved in regulating chloride ion flow across cell membranes, contributing to the maintenance of membrane potential and cellular homeostasis. These channels are expressed in various tissues, including the brain, intestines, and kidneys, and play a role in processes such as fluid secretion, neuronal excitability, and epithelial transport. By targeting ClC-2, GaTx2 is valuable for studying the physiological functions of chloride channels and exploring therapeutic possibilities for diseases linked to channel dysfunction, such as epilepsy, cystic fibrosis, and other channelopathies.

Current Research:

GaTx2 is a peptide toxin isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus, commonly known as the deathstalker scorpion. It functions as a high-affinity inhibitor of the ClC-2 chloride channel, a member of the voltage-gated chloride channel family involved in various physiological processes.
Structural Characteristics
GaTx2 is composed of 29 amino acid residues and stabilized by three disulfide bonds, contributing to its compact and stable structure. This configuration is characteristic of scorpion toxins that target ion channels.
Mechanism of Action
GaTx2 inhibits ClC-2 channels with an apparent dissociation constant (K_D) of approximately 20 picomolar (pM), indicating extremely high affinity. It exerts its inhibitory effect by increasing the latency to the first opening of the channel by nearly eightfold, thereby slowing channel activation. Notably, GaTx2 does not inhibit channels that are already open, suggesting that it specifically targets the activation gating mechanism of ClC-2.
Selectivity
GaTx2 exhibits high specificity for ClC-2 channels and shows no inhibitory effect on other chloride channels, such as ClC-0, ClC-1, ClC-3, and ClC-4, as well as on voltage-gated potassium channels. This selectivity makes it a valuable pharmacological tool for studying ClC-2 function without off-target effects.
Research Applications
Due to its high affinity and specificity, GaTx2 is utilized in research to probe the structure and function of ClC-2 channels. It aids in understanding the physiological roles of ClC-2 in various tissues and can be instrumental in exploring therapeutic targets for conditions where ClC-2 is implicated.
Conclusion
GaTx2 stands as the first peptide toxin identified to inhibit a ClC protein, offering a potent and selective means to investigate ClC-2 channels. Its discovery has provided significant insights into chloride channel pharmacology and continues to be a crucial tool in ion channel research.

Reference:

Thompson, C. H., Freeman, C. S., French, R. J., & McCarty, N. A. (2009). Pharmacological characterization of GaTx2, a peptide inhibitor of ClC-2 chloride channels. Biophysical Journal, 96(3), 470a.