Interaction of Mg2+ and phencyclidine in use-dependent block of NMDA channels

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The interaction between Mg2+ and phencyclidine (PCP) in blocking open N-methyl-d-aspartate (NMDA) channels was investigated in Xenopus oocytes injected with rat brain mRNA. These receptors exhibit the pharmacological and physiological properties of the neuronal receptors, and the oocyte is readily amenable to electrical recording and application of well-controlled chemical stimuli. We found that Mg2+ at physiological concentrations greatly impeded the ability of PCP to block the NMDA channel. The interaction between Mg2+ and PCP was competitive; 0.5 mM Mg2+ caused a four-fold decrease in the potency of PCP in blocking open NMDA channels. Moreover, Mg2+ speeded the recovery from PCP block in the presence of agonist, suggesting that Mg2+ reduced reblock of NMDA channels by PCP that had escaped from open channels. Our observations suggest that the presence of Mg2+ in the channel tends to prevent PCP entry and block. Since depolarization is likely to reduce channel occupancy by Mg2+ more than that by PCP, neural activity may have an important influence on the actions of PCP and related drugs.

Original languageEnglish (US)
Pages (from-to)187-191
Number of pages5
JournalNeuroscience Letters
Volume123
Issue number2
DOIs
StatePublished - Feb 25 1991

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Phencyclidine
Aspartic Acid
Oocytes
Xenopus
Pharmacology
Messenger RNA
Brain
Pharmaceutical Preparations

Keywords

  • Excitatory amino acid receptor
  • Glutamate receptor
  • Open channel block
  • Xenopus oocyte

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Interaction of Mg2+ and phencyclidine in use-dependent block of NMDA channels. / Lerma, Juan; Zukin, R. Suzanne; Bennett, Michael V. L.

In: Neuroscience Letters, Vol. 123, No. 2, 25.02.1991, p. 187-191.

Research output: Contribution to journalArticle

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abstract = "The interaction between Mg2+ and phencyclidine (PCP) in blocking open N-methyl-d-aspartate (NMDA) channels was investigated in Xenopus oocytes injected with rat brain mRNA. These receptors exhibit the pharmacological and physiological properties of the neuronal receptors, and the oocyte is readily amenable to electrical recording and application of well-controlled chemical stimuli. We found that Mg2+ at physiological concentrations greatly impeded the ability of PCP to block the NMDA channel. The interaction between Mg2+ and PCP was competitive; 0.5 mM Mg2+ caused a four-fold decrease in the potency of PCP in blocking open NMDA channels. Moreover, Mg2+ speeded the recovery from PCP block in the presence of agonist, suggesting that Mg2+ reduced reblock of NMDA channels by PCP that had escaped from open channels. Our observations suggest that the presence of Mg2+ in the channel tends to prevent PCP entry and block. Since depolarization is likely to reduce channel occupancy by Mg2+ more than that by PCP, neural activity may have an important influence on the actions of PCP and related drugs.",
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AB - The interaction between Mg2+ and phencyclidine (PCP) in blocking open N-methyl-d-aspartate (NMDA) channels was investigated in Xenopus oocytes injected with rat brain mRNA. These receptors exhibit the pharmacological and physiological properties of the neuronal receptors, and the oocyte is readily amenable to electrical recording and application of well-controlled chemical stimuli. We found that Mg2+ at physiological concentrations greatly impeded the ability of PCP to block the NMDA channel. The interaction between Mg2+ and PCP was competitive; 0.5 mM Mg2+ caused a four-fold decrease in the potency of PCP in blocking open NMDA channels. Moreover, Mg2+ speeded the recovery from PCP block in the presence of agonist, suggesting that Mg2+ reduced reblock of NMDA channels by PCP that had escaped from open channels. Our observations suggest that the presence of Mg2+ in the channel tends to prevent PCP entry and block. Since depolarization is likely to reduce channel occupancy by Mg2+ more than that by PCP, neural activity may have an important influence on the actions of PCP and related drugs.

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