PE 22-28 is a peptide inhibitor of the two-pore domain potassium channel K2P2.1/TREK1 (IC50 = 0.1 nM in HEK293 cells expressing the human channel) and a fragment of spadin. It is selective for K2P2.1/TREK1 over K2P10.1 /TREK2, K2P13.1/TRAAK, K2P18.1/TRESK, and K2P3.1/TASK1 in HEK293 cells expressing the human channels at 100 nM. It promotes neurogenesis, increasing Psd-95 levels in mouse hippocampi and enhancing synaptogenesis. At 0.3 μg/kg for four days, PE 22-28 improves mouse behavior in tests like the forced swim test, novelty-suppressed feeding, and Porsolt learned helplessness test, suggesting potential for treating depression.
