title: A-kinase anchoring protein 150 expression in a specific subset of TRPV1- and CaV 1.2-positive nociceptive rat dorsal root ganglion neurons.
abstract: Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and phosphatases by the scaffolding A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 has been implicated in inflammatory pain by targeting protein kinase A (PKA) and protein kinase C (PKC) to the transient receptor potential vanilloid 1 (TRPV1) channel in peripheral sensory neurons, thus lowering threshold for activation of the channel by multiple inflammatory reagents. However, the expression pattern of AKAP150 in peripheral sensory neurons is unknown. Here we identify the peripheral neuron subtypes that express AKAP150, the subcellular distribution of AKAP150, and the potential target ion channels in rat dorsal root ganglion (DRG) slices. We found that AKAP150 is expressed predominantly in a subset of small DRG sensory neurons, where it is localized at the plasma membrane of the soma, axon initial segment, and small fibers. Most of these neurons are peripherin positive and produce C fibers, although a small portion produce Aδ fibers. Furthermore, we demonstrate that AKAP79/150 colocalizes with TRPV1 and Ca(V) 1.2 in the soma and axon initial segment. Thus AKAP150 is expressed in small, nociceptive DRG neurons, where it is targeted to membrane regions and where it may play a role in the modulation of ion channel phosphorylation states required for hyperalgesia.
authors.affiliation: Program in Neuroscience, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Brandao
authors.forename: Mark L
authors.initials: ML
authors.lastname: Dell'Acqua
authors.forename: S Rock
authors.initials: SR
authors.lastname: Levinson
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000378:metabolism*; D020864:Calcium Channels, N-Type
chemical_list: D054758:A Kinase Anchor Proteins; D015220:Calcium Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D050916:TRPV Cation Channels; C415703:Akap5 protein, rat; C491367:Cacna1a protein, rat; D020864:Calcium Channels, N-Type; C493922:Trpv1 protein, rat