Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation.
The roles of N-methyl-D-aspartate (NMDA) receptors and protein kinase C (PKC) are critical in generating and maintaining a variety of sustained neuronal responses. In the nociceptive (pain-sensing) system, tissue injury or repetitive stimulation of small-diameter afferent fibres triggers a dramatic increase in discharge (wind-up) or prolonged depolarization of spinal cord neurons. This central sensitization can neither be induced nor maintained when NMDA receptor channels are blocked. In the trigeminal subnucleus caudalis (a centre for processing nociceptive information from the orofacial areas), a mu-opioid receptor agonist causes a sustained increase in NMDA-activated currents by activating intracellular PKC. There is also evidence that PKC enhances NMDA-receptor-mediated glutamate responses and regulates long-term potentiation of synaptic transmission. Despite the importance of NMDA-receptors and PKC, the mechanism by which PKC alters the NMDA response has remained unclear. Here we examine the actions of intracellularly applied PKC on NMDA-activated currents in isolated trigeminal neurons. We find that PKC potentiates the NMDA response by increasing the probability of channel openings and by reducing the voltage-dependent Mg2+ block of NMDA-receptor channels.
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77550.
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005246:Feedback; D007051:Ibotenic Acid / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007608:Kainic Acid; D008274:Magnesium / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D014275:Trigeminal Caudal Nucleus / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011493:Protein Kinase C; D008274:Magnesium; D007608:Kainic Acid