Acetylcholine-dependent upregulation of TASK-1 channels in thalamic interneurons by a smooth muscle-like signalling pathway.
Michael LeistSusanne RinnéMaia DatunashviliAnia AissaouiHans-Christian PapeNiels DecherSven G MeuthThomas BuddePublished in: The Journal of physiology (2017)
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 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 induces IN hyperpolarization by recruiting the G-protein βγ subunit (Gβγ), class-1A phosphatidylinositol-4,5-bisphosphate 3-kinase, and cellular and sarcoma (c-Src) tyrosine kinase, 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 as well as an increase in the intracellular level of phosphatidylinositol-3,4,5-trisphosphate facilitated the muscarinic effect. Our results have uncovered a previously unknown role of c-Src tyrosine kinase in regulating IN function in the brain and identified a novel mechanism by which TASK-1 channels are activated in neurons.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- smooth muscle
- spinal cord
- protein kinase
- resting state
- deep brain stimulation
- signaling pathway
- cerebral ischemia
- single cell
- functional connectivity
- neuropathic pain
- optical coherence tomography
- diabetic retinopathy
- cell proliferation
- poor prognosis
- cell therapy
- minimally invasive
- health information
- blood brain barrier
- spinal cord injury
- brain injury
- social media
- optic nerve