Trends in Neurosciences
ReviewThe TASK background K2P channels: chemo- and nutrient sensors
Section snippets
Oxygen sensing in the carotid body glomus cells
In response to environmental hypoxia, there is a rapid, reflex increase in the respiration rate 14, 29. The primary sensory glomus cells (type I) of the carotid body respond to hypoxia and acidosis with depolarization that initiates electrical activity, Ca2+ entry and neurosecretion (Figure 2a,b). The type I cells activate afferent sensory fibers of the sinus nerve, which in turn stimulate brainstem respiratory centers, culminating in enhanced ventilation (Figure 2a). A key ionic current
Acid sensing in the brainstem
Central chemoreception is the homeostatic process by which pH variations in the brainstem, caused by increased levels of CO2, contribute to changes in the depth and frequency of breathing, and thereby elimination of CO2. Many neurons within the respiratory control system in the brainstem might contribute to this pH sensitivity (Figure 3a).
Specialized neurons located at the ventral surface of the medulla oblongata, in the retrotrapezoid nucleus, serve as sensors for CO2/pH [15]. These neurons
Glucose and CO2/pH sensing in the hypothalamic orexin neurons
Glucose homeostasis is essential for brain function, as glucose is the primary fuel for neurons. Specific neurons, including the hypothalamic orexin neurons, are able to sense glucose and trigger adaptive behavioral responses. Orexin neurons have been identified in situ in a transgenic mouse expressing enhanced green fluorescent protein (eGFP) driven by the human pre-pro-orexin promoter. These neurons express both TASK-1 and TASK-3 subunits [27] (Figure 3d). The activity of these hypothalamic
Conclusions
Taken together, these recent studies suggest that both TASK-1 and TASK-3 subunits play an important functional role in chemo- and nutrient-sensing integrating multiple physiological stimuli, including hypoxia, acidosis and glucose levels. For instance, the inhibition of TASK channels in brainstem respiratory neurons and glomus cells in the carotid body by acidic and/or hypoxic stimuli plays a central role in initiating the reflex increase in ventilation. By contrast, stimulation of TASK
Future directions
Although major progress has been made recently in the biophysical and pharmacological characterization of the TASK K2P channels in chemosensitive cells, several important issues remain to be addressed including: (i) Which subunits constitute the heteromeric TASK complex in chemosensitive cells? (ii) Is the chemo- and glucose sensitivity altered in the TASK-1, TASK-3 and TASK-1–TASK-3 double knockout mice? (iii) What is the identity of the oxygen sensor(s) regulating TASK channels? (iv) What is
Acknowledgements
We are grateful to the ANR 2005 Cardiovasculaire-obésité-diabète, to the Association for Information and Research on Genetic Kidney Disease France, to the Fondation del Duca, to the Fondation de France, to the Fondation de la Recherche Médicale, to EEC Marie-Curie fellowships, to the Fondation de Recherche sur l’Hypertension Artérielle, to AFM, to HFSP to INSERM and to CNRS for support. We thank Douglas Bayliss and Keith Buckler for their constructive input and personal communications.
Glossary
- 4-aminopryridine (4-AP)
- a blocker of Kv channels.
- AMP-activated protein kinase (AMPK)
- this enzyme induces a cascade of events in response to an increase in AMP concentration, reflecting the energy status of the cell. AMPK-mediated phosphorylation switches cells from ATP consumption to ATP production. AMPK also regulates insulin synthesis and secretion in pancreatic islet β-cells as well as modulation of hypothalamic functions. AMPK is expressed in glomus cells in the carotid body.
- Cell-attached
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Cited by (67)
Anti-hypoxic effect of interleukin-10 in hippocampal neurons is mediated by modulation of TASK-1 and TASK-3 channels activity
2022, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Thus, we suggested that anti-hypoxic effect of IL-10 might be mediated by modulation of certain type of ion channels that are sensitive to hypoxic episode. It is known that members of two-pore (2P-domain; K2p) potassium channels family as TWIK -related acid-sensitive K+ channels (TASK) are sensitive to oxygen, acidosis, and hypoxia [8–10]. TASK channels are responsible for K+ background leak current (Ileak) which is critical for maintenance of resting membrane potential and for regulation of neuronal excitability [11,12].
HCN and K <inf>2P</inf> Channels in Anesthetic Mechanisms Research
2018, Methods in EnzymologyCitation Excerpt :If using the pcDNA3.1(+)IRES GFP vector, the degree of GFP fluorescence roughly correlates with K2P expression level, allowing the experimenter to avoid patching cells that either under or overexpress the K2P of interest. A number of groups have studied K2P activity in isolated dorsal root ganglion cells and in other native tissues (Alloui et al., 2006; Duprat, Lauritzen, Patel, & Honoré, 2007). These studies can be complicated to interpret due to cell-type variation in K2P modulatory factors (PIP2, arachidonic acid, PKA, and PKC activity) known to alter channel activity and coexpression of multiple K2P subtypes in a single cell.
Acid-sensing ion channels in gastrointestinal function
2015, NeuropharmacologyCitation Excerpt :Being primarily background channels, K2P channels subserve a key function in setting the resting membrane potential and thereby the excitability of neurons. Many of the K2P channels such as TASK-1, TASK-2, TASK-3, TRESK, TREK-1, TREK-2 and TRAAK are expressed by sensory neurons and react to modifications of intra- and/or extracellular pH (Goldstein et al., 2005; Duprat et al., 2007; Holzer, 2009). The activity of other K+ channels such as distinct members of the inward rectifier K+ channel (Kir) family (Kir1.1, Kir4.1, Kir5.1 and Kir6.1) and of the voltage-activated K+ channel (Kv) family (Kv1.3, Kv1.4 and Kv11.1) is also modified by extracellular acidification, as is the case with nifedipine-sensitive L-type Ca2+ channels and distinct voltage-gated Na+ channels (Holzer, 2009).
N-glycosylation-dependent control of functional expression of background potassium channels K<inf>2P</inf>3.1 and K<inf>2P</inf>9.1
2013, Journal of Biological ChemistryCitation Excerpt :It has been suggested that extracellular lectins may play a role in binding HK-ATPase and stabilizing it at the cell surface (37). Glycosylation increases thermodynamic stability by reducing the amount of surface area accessible to solvent, which in turn influences structural dynamics and protein function (26); this effect has been clearly demonstrated for the thermostability of human aquaporin 10 protein (39). Although a number of potential mechanisms exist, it will be important to find out how glycosylation contributes to the stability of K2P3.1 and to determine the process that renders K2P9.1 less sensitive to this regulation.
The PFC-LH-VTA pathway contributes to social deficits in IRSp53-mutant mice
2023, Molecular Psychiatry