PE-22-28

Spadin and the TREK-1 hypothesis

TREK-1 is a background potassium channel encoded by KCNK2. Rodent work reported that animals lacking TREK-1 display a phenotype resembling that produced by serotonergic antidepressants, which made pharmacological blockade of the channel an attractive research question. Spadin, released during sortilin maturation, was identified as an endogenous blocker; PE-22-28 is the minimal active fragment mapped from that sequence.

Electrophysiological characterization

• Whole-cell patch-clamp recordings measuring TREK-1 current inhibition in transfected cell lines
• Selectivity panels comparing activity at related two-pore-domain channels such as TRAAK and TASK
• Concentration-response profiling used to establish potency relative to full-length spadin

Behavioral and plasticity endpoints

Evidence status

Analytical practice

The tryptophan residue in the sequence gives usable 280 nm absorbance, which makes spectrophotometric concentration checks straightforward alongside HPLC quantification. Net peptide content and counterion values from the certificate of analysis should still be applied when normalizing stocks, since the difference between gross and net peptide mass is easily large enough to shift a concentration-response curve by a meaningful margin.

Keep the sealed vial at −20 °C, protected from light and moisture, and let it warm to room temperature before opening so condensation does not reach the powder. Reconstitute with bacteriostatic or sterile water added slowly down the inner wall of the vial, swirling gently until the cake dissolves; do not shake or vortex. Store the resulting solution at 2–8 °C, protected from light, and label it with concentration and date. Short linear peptides with free termini degrade faster in solution than protected analogs, so prepare single-use aliquots and keep working samples on ice during electrophysiology or assay sessions.