Acetylcholine-dependent upregulation of TASK-1 channels in thalamic interneurons by a smooth muscle-like signalling pathway

Autor: Niels Decher, Sven G. Meuth, Ania Aissaoui, Hans-Christian Pape, Thomas Budde, Susanne Rinné, Michael Leist, Maia Datunashvili
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Physiology. 595:5875-5893
ISSN: 0022-3751
DOI: 10.1113/jp274527
Popis: The dorsal part of the lateral geniculate nucleus (dLGN) is the main thalamic site for state-dependent transmission of visual information. Non-retinal inputs from the ascending arousal system and inhibition provided by γ-aminobutyric acid (GABA)ergic local circuit interneurons (INs) control neuronal activity within the dLGN. In particular, acetylcholine (ACh) depolarizes thalamocortical relay (TC) neurons by inhibiting two-pore domain potassium (K2P) channels. Conversely, ACh also hyperpolarizes INs via an as-yet-unknown mechanism. By using whole cell patch-clamp recordings in brain slices and appropriate pharmacological tools we here report that stimulation of type 2 muscarinic ACh receptors (M2AChRs) induces IN hyperpolarization by recruiting the G beta-gamma complex (Gβγ), class-1A phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and cellular and sarcoma (c-Src) tyrosine kinase (TK), leading to activation of two-pore domain weakly inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ (TASK)-1 channels. The latter was confirmed by the use of TASK-1 deficient mice. Furthermore inhibition of phospholipase Cβ (PLCβ) as well as an increase in the intracellular level of phosphatidylinositol-3,4,5-trisphosphate (PIP3) facilitated the muscarinic effect. Our results have uncovered a previously unknown role of c-Src TK in regulating IN function in the brain and identified a novel mechanism by which TASK-1 channels are activated in neurons. This article is protected by copyright. All rights reserved
Databáze: OpenAIRE
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