Methods for inhibiting CLC-2 channel with GATX2
Compositions and methods of using scorpion venom peptide that is a ligand for ClC channels are provided. One aspect provides a pharmaceutical composition containing an amount of GaTx2 effective to inhibit ClC activity. Methods of treating a disorder or symptom of a disorder related to aberrant ClC channel activity are also provided.
1. A method for inhibiting activity of a ClC-2 channel in a subject comprising administering to the subject an isolated peptide having at least 95% sequence identity to SEQ ID NO:1, wherein the variation in amino acid sequence is due to a single conservative amino acid substitution, wherein the isolated peptide reduces chloride transport through the ClC-2 channel, and wherein the subject has diarrhea-predominant inflammatory bowel syndrome or secretory diarrhea.
2. The method of claim 1 , wherein the isolated peptide has an apparent dissociation constant of about 12 pM for ClC-2 at −100 mV.
3. The method of claim 1 , wherein the isolated peptide is approximately a 3.2 kDa peptide.
4. The method of claim 1 , wherein the isolated peptide has a calculated pI of 4.51.
5. The method of claim 1 , wherein the isolated peptide is synthetic or recombinant.
6. The method of claim 1 , wherein the isolated peptide is administered in a dosage form.
7. The method of claim 1 , wherein the isolated peptide is isolated from venom from Leiurus quinquestriatus hebraeus.