AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

Sraboni Chaudhury, Manjot Bal, Sergei Belugin, Mark S. Shapiro, Nathaniel A. Jeske

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1.Results: In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity.Conclusions: the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.

Original languageEnglish (US)
Article number34
JournalMolecular Pain
Volume7
DOIs
StatePublished - May 14 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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    Chaudhury, S., Bal, M., Belugin, S., Shapiro, M. S., & Jeske, N. A. (2011). AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin. Molecular Pain, 7, [34]. https://doi.org/10.1186/1744-8069-7-34