Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation

Li Chen, Li-Yen Huang

Research output: Contribution to journalArticle

785 Citations (Scopus)

Abstract

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 (painsensing) 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 blocked1,2. In the trigeminal subnucleus caudalis (a centre for processing nociceptive information from the orofacial areas3), a μ-opioid receptor agonist causes a sustained increase in NMDA-activated currents by activating intracellular PKC4. There is also evidence that PKC enhances NMDA-receptor-mediated glutamate responses4-7 and regulates long-term potentiation of synaptic transmission8-14. 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 voltagedependent Mg2+ block of NMDA-receptor channels.

Original languageEnglish (US)
Pages (from-to)521-523
Number of pages3
JournalNature
Volume356
Issue number6369
StatePublished - Apr 9 1992

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N-Methyl-D-Aspartate Receptors
Protein Kinase C
N-Methylaspartate
Aspartate Kinase
Central Nervous System Sensitization
Neurons
Long-Term Potentiation
Opioid Receptors
Automatic Data Processing
Glutamic Acid
Spinal Cord
Wounds and Injuries

ASJC Scopus subject areas

  • General

Cite this

Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. / Chen, Li; Huang, Li-Yen.

In: Nature, Vol. 356, No. 6369, 09.04.1992, p. 521-523.

Research output: Contribution to journalArticle

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AB - 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 (painsensing) 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 blocked1,2. In the trigeminal subnucleus caudalis (a centre for processing nociceptive information from the orofacial areas3), a μ-opioid receptor agonist causes a sustained increase in NMDA-activated currents by activating intracellular PKC4. There is also evidence that PKC enhances NMDA-receptor-mediated glutamate responses4-7 and regulates long-term potentiation of synaptic transmission8-14. 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 voltagedependent Mg2+ block of NMDA-receptor channels.

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