Selectivity filter gating in homomeric and heteromeric K+ channels
In the first funding period of FOR 2518 (DynIon) we investigated the selectivity filter (SF) gating properties in homomeric K2P and other K+ channels and thereby discovered a novel class of pharmacological activators -termed NCAs (Negatively Charged Activators)- that target the apparently highly conserved gating machinery of the SF in different classes of K+ channels including many K2P channels, voltage-gated hERG channels and Ca2+‑activated BK-type K+ channels.
In the second funding period we plan to investigate the pharmacological and physiological gating stimuli/mechanisms that control the SF gate in various K+ channels, with special focus on homomeric and heteromeric K2P channels. By usage of different techniques and approaches like mutagenesis, electrophysiological and fluorescence measurements as well as full atomistic molecular dynamics (MD) simulations we plan to characterize functional K2P channel heterodimers regarding their structure-function relationships, gating properties and pharmacology.
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Prof. Dr. Thomas Baukrowitz
24118 Kiel
Dr. Marcus Schewe