title: Subthreshold membrane potential oscillation mediates the excitatory effect of norepinephrine in chronically compressed dorsal root ganglion neurons in the rat.
abstract: Injured dorsal root ganglion (DRG) neurons often develop adrenergic sensitivity. To investigate the mechanisms of this phenomenon, the effects of norepinephrine (NE) on membrane potential of large- and medium-sized A-type neurons from chronically compressed DRG were recorded electrophysiologically in vitro. NE induced a depolarization in both control (26/36) and injured (56/62) neurons, whereas the incidence and amplitude of NE-induced depolarization in the injured neurons were significantly higher than that in controls. Following NE-induced depolarization, a subthreshold membrane potential oscillation (SMPO) was triggered or enhanced that initiated or increased repetitive firing in a fraction of injured neurons (15/56). After the SMPO was selectively abolished by application of tetrodotoxin (TTX), NE-induced depolarization failed to produce repetitive firing, even with a greater depolarization. Application of Rp-cAMPS (500 microM), a selective inhibitor of protein kinase A (PKA), decreased both SMPO and repetitive firing evoked by NE application or by intracellular current injection. Conversely, Sp-cAMPS (500 microM), a PKA activator, had a facilitating effect on both the SMPO and the repetitive firing. These results strongly suggest that a PKA mediated triggering and enhancement of SMPO may be responsible for the excitatory effects of NE on sensory neurons in neuropathic rats.
mesh_terms: D000818:Animals; D002908:Chronic Disease; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004056:Differential Threshold; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009408:Nerve Compression Syndromes / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009991:Oscillometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D013779:Tetrodotoxin; D000242:Cyclic AMP; D009638:Norepinephrine