AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

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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 read more 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 click here 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.