Differential contribution of THIK-1 K⁺ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia.

ABSTRACT: Neuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K⁺ efflux as a key signaling event, suggesting that K⁺-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K⁺ channels and P2X7 receptors, but their interactions and potential therapeutic role in the human brain are unknown. Using a novel specific inhibitor of THIK-1 in combination with patch-clamp electrophysiology in slices of human neocortex, we found that THIK-1 generated the main tonic K⁺ conductance in microglia that sets the resting membrane potential. Extracellular ATP stimulated K

SUBMITTER: Rifat A 

PROVIDER: S-EPMC10895799 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature