Protein kinase A modulates spontaneous activity in chronically compressed dorsal root ganglion neurons in the rat.
Protein kinase A (PKA) can play a critical role in the modulation of neuronal excitability. We examined the role of PKA in the modulation of abnormal spontaneous activity (SA) originating from the chronically compressed dorsal root ganglion (CCD). The L(4) and L(5) dorsal root ganglia (DRGs) were compressed by inserting a stainless steel rod into each corresponding intervertebral foramen. After 1-14 postoperative days, SA in DRG neurons with myelinated axons was recorded in vitro from teased dorsal root microfilaments. Rp-cAMPS (5-500 microM), a specific inhibitor of PKA, caused a dose-dependent decrease in the discharge rate of SA when topically applied to the DRG. The highest dose completely blocked the SA, but not the conduction of action potentials. H89 (10 microM), another PKA inhibitor, also markedly decreased SA. Sp-cAMPS (500 microM), a specific activator of PKA, increased the discharge rate of SA in all injured units tested, but did not trigger firing in silent neurons. Okadaic acid (0.1 microM), a protein phosphatase inhibitor, and forskolin (1 microM), an adenyl cyclase activator, each significantly increased the discharge rate of SA. These results strongly suggest that PKA modulates the SA in injured DRG neurons with myelinated axons.
Hu
San-Jue
SJ
Department of Anesthesiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8051, USA.
Song
Xue-Jun
XJ
Greenquist
Kenneth W
KW
Zhang
Jun-Ming
JM
LaMotte
Robert H
RH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D009408:Nerve Compression Syndromes / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases