8uec
From Proteopedia
Structure of TREK-1CG*:CAT335a
Structural highlights
FunctionKCNK2_MOUSE Ion channel that contributes to passive transmembrane potassium transport. Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner. In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2 (PubMed:24496152). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (PubMed:24496152).[1] [2] [3] [4] Publication Abstract from PubMedK(2P) potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K(2P) function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (covalent activation of TREK family K(+) channels to clamp membrane potential) that leverages the discovery of a K(2P) modulator pocket site that reacts with electrophile-bearing derivatives of a TREK subfamily small-molecule activator, ML335, to activate the channel irreversibly. We show that CATKLAMP can be used to probe fundamental aspects of K(2P) function, as a switch to silence neuronal firing, and is applicable to all TREK subfamily members. Together, our findings exemplify a means to alter K(2P) channel activity that should facilitate molecular and systems level studies of K(2P) function and enable the search for new K(2P) modulators. Development of covalent chemogenetic K(2P) channel activators.,Deal PE, Lee H, Mondal A, Lolicato M, Mendonca PRF, Black H, Jang S, El-Hilali X, Bryant C, Isacoff EY, Renslo AR, Minor DL Jr Cell Chem Biol. 2024 Jul 18;31(7):1305-1323.e9. doi: , 10.1016/j.chembiol.2024.06.006. PMID:39029456[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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