Involvement of intracellular calcium and protein phosphatases in long-term depression of A-fiber-mediated primary afferent neurotransmission.
Long-term depression (LTD) of monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) in substantia gelatinosa (SG) neurons can be induced by brief high-frequency electrical stimulation (HFS, 300 pulses at 100 Hz) of primary afferent fibers in dorsal roots. Here we examined the possible cellular mechanism underlying spinal LTD. Conventional intracellular recordings were made from SG neurons in a transverse slice-dorsal root preparation of the young rat lumbar spinal cord. LTD of both monosynaptic and polysynaptic EPSPs was induced in 16 of 24 SG neurons by HFS of dorsal root in either the presence or absence of the GABA(A) receptor antagonist bicuculline and the glycine receptor antagonist strychnine. Loading the postsynaptic cell with BAPTA, an intracellular Ca(2+) chelator, almost completely blocked the induction of LTD. Induction of LTD was abolished by bath application of calyculin A (100 nM), a potent inhibitor of protein phosphatases 1 and 2A. These results indicate that: (i) a rise in postsynaptic Ca(2+) is necessary for LTD induction, (ii) synaptic activation of protein phosphatases 1 and 2A plays an important role in the induction of LTD of primary afferent A-fiber neurotransmission in the young rat spinal cord, and (iii) the effect of LTD may be physiologically relevant for transmission and integration of sensory information, including nociception.
Cheng
Gong
G
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011-1250, USA. gong_cheng@iastate.edu
Randić
Mirjana
M
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017097:Electric Impedance; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D005110:Extracellular Space / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008387:Marine Toxins; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D019347:Potassium Acetate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000494:pharmacology; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission; D013997:Time Factors
D002614:Chelating Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D018684:Glycine Agents; D008387:Marine Toxins; D010080:Oxazoles; D004533:Egtazic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D013331:Strychnine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D019347:Potassium Acetate; D002118:Calcium; D001640:Bicuculline