Cellular and Molecular Neurobiology

, Volume 30, Issue 4, pp 505–509

The Cdk5 Kinase Downregulates ATP-Gated Ionotropic P2X3 Receptor Function Via Serine Phosphorylation

  • Asha Nair
  • Manuela Simonetti
  • Elsa Fabbretti
  • Andrea Nistri
Short Communication


Cdk5 is an endogenous kinase activated by the neuronal-specific protein p35 and implicated in multiple neuronal functions, including modulation of certain pain responses. We investigated whether Cdk5 could regulate ATP-gated P2X3 receptors that are members of the family of membrane proteins expressed by sensory neurons to transduce nociception in baseline and chronic pain. To study the potential P2X3 receptor modulation by Cdk5, we co-transfected rat P2X3 receptors and Cdk5 into HEK cells and observed increased P2X3 receptor serine phosphorylation together with downregulation of receptor currents only when these genes were transfected together with the gene of the Cdk5 activator p35. The changes in receptor responses were limited to depressed current amplitude as desensitization and recovery were not altered. Transfection of p35 with P2X3 similarly downregulated receptor responses, suggesting that this phenomenon could be observed even with constitutive Cdk5. The present data indicate a novel target to express the action of Cdk5 on membrane proteins involved in pain perception.


Purinergic receptors Receptor modulation Patch clamp Serine/threonine kinase p35 HEK cells 


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Asha Nair
    • 1
  • Manuela Simonetti
    • 1
    • 3
  • Elsa Fabbretti
    • 1
    • 2
  • Andrea Nistri
    • 1
  1. 1.Neurobiology Sector and Italian Institute of Technology UnitInternational School for Advanced Studies (SISSA)TriesteItaly
  2. 2.University of Nova GoricaNova GoricaSlovenia
  3. 3.Pharmacology Institute, Faculty of MedicineUniversity of HeidelbergHeidelbergGermany

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