Paper Search Console

Home Search Page About Contact

Journal Title

Title of Journal: Pflugers Arch Eur J Physiol

Search In Journal Title:

Abbravation: Pflügers Archiv - European Journal of Physiology

Search In Journal Abbravation:

Publisher

Springer Berlin Heidelberg

Search In Publisher:

DOI

10.1002/cncr.24684

Search In DOI:

ISSN

1432-2013

Search In ISSN:
Search In Title Of Papers:

Allosteric regulation of the P2X4 receptor channel

Authors: Hana Zemkova Anmar Khadra Milos B Rokic Vendula Tvrdonova Arthur Sherman Stanko S Stojilkovic
Publish Date: 2014/06/11
Volume: 467, Issue: 4, Pages: 713-726
PDF Link

Abstract

Allosteric modulators of ligandgated receptor channels induce conformational changes of the entire protein that alter potencies and efficacies for orthosteric ligands expressed as the half maximal effective concentration EC50 and maximum current amplitude respectively Here we studied the influence of allostery on channel pore dilation an issue not previously addressed Experiments were done using the rat P2X4 receptor expressed in human embryonic kidney 293T cells and gated by adenosine 5triphosphate ATP in the presence and absence of ivermectin IVM an established positive allosteric regulator of this channel In the absence of IVM this channel activates and deactivates rapidly does not show transition from open to dilated states desensitizes completely with a moderate rate and recovers only fractionally during washout IVM treatment increases the efficacy of ATP to activate the channel and slows receptor desensitization during sustained ATP application and receptor deactivation after ATP washout The rescue of the receptor from desensitization temporally coincides with pore dilation and the dilated channel can be reactivated after washout of ATP Experiments with vestibular and transmembrane domain receptor mutants further established that IVM has distinct effects on opening and dilation of the channel pore the first accounting for increased peak current amplitude and the latter correlating with changes in the EC50 and kinetics of receptor deactivation The corresponding kinetic Markov state model indicates that the IVMdependent transition from open to dilated state is coupled to receptor sensitization which rescues the receptor from desensitization and subsequent internalization Allosterically induced sensitization of P2X4R thus provides sustained signaling during prolonged and repetitive ATP stimulationThis study was supported by the Grant Agency of the Czech Republic P304/12/G069 Grant Agency of Charles University 3446/2011 the project “BIOCEV” – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University CZ105/1100/020109 the Natural Sciences and Engineering Council of Canada NSERC discovery grant to AK and the Intramural Research Program of the NICHD and NIDDK NIH

Keywords:

References

.
Search In Abstract Of Papers:
Other Papers In This Journal:
  1. Evaluation of biomechanical status of dysplastic human hips
  2. Molecular physiology of EAAT anion channels
  3. Initial charge distribution and capacity transients in frog skeletal muscle
  4. How steroid hormones act on the endothelium—insights by atomic force microscopy
  5. Effects of temperature on pacemaker potentials in the mouse small intestine
  6. Glutathione peroxidase 1 protects mitochondria against hypoxia/reoxygenation damage in mouse hearts
  7. High glucose inhibits HCO 3 − and fluid secretion in rat pancreatic ducts
  8. Possibilities for clinical use of prostacyclin in vascular disease
  9. Glutathione peroxidase 1 protects mitochondria against hypoxia/reoxygenation damage in mouse hearts
  10. Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis
  11. From taste to touch: sensory signaling in model organisms
  12. Expression and function of K v 7 channels in murine myometrium throughout oestrous cycle
  13. Regulation of voltage-gated sodium current by endogenous Src family kinases in cochlear spiral ganglion neurons in culture
  14. Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport
  15. Macrophages in vascular inflammation and atherosclerosis
  16. Sex differences in cardiac autonomic regulation and in repolarisation electrocardiography
  17. Endoplasmic reticulum–mitochondria coupling: local Ca 2+ signalling with functional consequences
  18. Intercellular and extracellular mechanotransduction in cardiac myocytes
  19. Overexpression of inducible 70-kDa heat shock protein in mouse improves structural and functional recovery of skeletal muscles from atrophy
  20. Antagonism of stromal cell-derived factor-1α reduces infarct size and improves ventricular function after myocardial infarction
  21. Role of smooth muscle cell mineralocorticoid receptor in vascular tone
  22. Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation
  23. P2X 3 receptor gating near normal body temperature
  24. Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice
  25. Pathophysiology of HCN channels
  26. Dynamic modulation of intracellular glucose imaged in single cells using a FRET-based glucose nanosensor
  27. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress
  28. Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc Min/+ mouse
  29. lnterleukin-6 (IL-6) and soluble receptors for interleukin-2 (slL-2R) in the diagnosis of early severe infection in the critically ill newborns
  30. Regulation of mineral metabolism by lithium
  31. Enhancement of the Shaker B Δ6–46 current by fatty acids depends on the activation of the lipoxygenase metabolic pathway
  32. Contribution of calcium-conducting channels to the transport of zinc ions
  33. Role of bestrophin-1 in store-operated calcium entry in retinal pigment epithelium
  34. A brief history of trp : commentary and personal perspective
  35. Glutamate receptors, neurotoxicity and neurodegeneration
  36. The I Cl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP 2
  37. Localization of the ergtoxin-1 receptors on the voltage sensing domain of hERG K + channel by AFM recognition imaging
  38. Circadian variation in the effects of nitric oxide synthase inhibitors on body temperature, feeding and activity in rats
  39. Regulated acid–base transport in the collecting duct
  40. Piezo1-dependent regulation of urinary osmolarity
  41. AQP1 mediates water transport in the carotid body
  42. Closure of multiple types of K + channels is necessary to induce changes in renal vascular resistance in vivo in rats
  43. Adult nephron-specific MR-deficient mice develop a severe renal PHA-1 phenotype
  44. Enhanced desensitization followed by unusual resensitization in GABA A receptors in phospholipase C-related catalytically inactive protein-1/2 double-knockout mice
  45. Sensitisation of TRPV4 by PAR 2 is independent of intracellular calcium signalling and can be mediated by the biased agonist neutrophil elastase
  46. Opioid receptor-mediated effects of interleukin-2 on the [Ca 2+ ] i transient and contraction in isolated ventricular myocytes of the rat
  47. Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells
  48. SGK1 activity in Na + absorbing airway epithelial cells monitored by assaying NDRG1-Thr 346/356/366 phosphorylation
  49. Genistein inhibits voltage-gated sodium currents in SCG neurons through protein tyrosine kinase-dependent and kinase-independent mechanisms
  50. An Editor’s farewell!
  51. Effects of glucose, forskolin and tolbutamide on membrane potential and insulin secretion in the insulin-secreting cell line INS-1
  52. Inosine partially mimics the effects of glucose on ionic fluxes, electrical activity, and insulin release in mouse pancreatic B-cells
Search Result: