Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons

Zi Zhen Wu, Bing Cai Guan, Zhi Wang Li, Qing Yang, Chang Jin Liu, Jian Guo Chen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

This study aimed to explore the modulatory effect of substance P (SP) on the current response mediated by N-methyl-D-aspartate (NMDA) receptor in rat primary sensory neurons and its time course using whole-cell patch clamp technique. The majority of neurons (179/213, 84.0%) examined were sensitive to NMDA (0.1-1000 μM) with an inward current, and a proportion of the NMDA-sensitive neurons also responded to SP (78/98, 80.0%) with an inward current. Pretreatment with SP potentiated the NMDA-activated current (I NMDA) in a non-competitive manner, which is shown in that SP shifted the concentration-response curve for NMDA upwards compared with the control; the maximal value of INMDA increased fourfold, while the EC50 values for both curves were very close (28 vs. 30 μM). Furthermore, this potentiating effect was time-dependent: the amplitude of INMDA reached its maximum 20 min after SP preapplication, and thereafter maintained a steady level of about 2-3 times its control for 2 or even 3 h. This sustained potentiation by SP of INMDA could be blocked by extracellular application of WIN51708, a selective non-peptide antagonist of NK-1 receptor; and abolished by intracellular application of either BAPTA, or H-7, or KN-93. Though NMDA applied alone also induced a short-term (less than 20 min) self-potentiation of INMDA, it could be abolished by intracellular dialysis of BAPTA or KN-93 completely. As is known, the cell body of dorsal root ganglion (DRG) neurons is generally used as an accessible model for studying the characteristics of the membrane of primary afferent terminals in the dorsal horn of spinal cord. Therefore, these results may offer a clue to the explanation of the symptoms of chronic pain.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalBrain Research
Volume1010
Issue number1-2
DOIs
StatePublished - Jun 4 2004
Externally publishedYes

Fingerprint

Sensory Receptor Cells
N-Methylaspartate
Substance P
Neurons
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Neurokinin-1 Receptors
Spinal Ganglia
Patch-Clamp Techniques
N-Methyl-D-Aspartate Receptors
Chronic Pain
Dialysis
Membranes

Keywords

  • Excitable cells and synaptic transmission
  • Intracellular dialysis
  • NMDA-activated current
  • Presynaptic mechanisms
  • Primary sensory neuron
  • Rat
  • Substance P
  • Sustained potentiation
  • Whole-cell patch clamp

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Developmental Biology
  • Clinical Neurology

Cite this

Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons. / Wu, Zi Zhen; Guan, Bing Cai; Li, Zhi Wang; Yang, Qing; Liu, Chang Jin; Chen, Jian Guo.

In: Brain Research, Vol. 1010, No. 1-2, 04.06.2004, p. 117-126.

Research output: Contribution to journalArticle

Wu, Zi Zhen ; Guan, Bing Cai ; Li, Zhi Wang ; Yang, Qing ; Liu, Chang Jin ; Chen, Jian Guo. / Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons. In: Brain Research. 2004 ; Vol. 1010, No. 1-2. pp. 117-126.
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AU - Liu, Chang Jin

AU - Chen, Jian Guo

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AB - This study aimed to explore the modulatory effect of substance P (SP) on the current response mediated by N-methyl-D-aspartate (NMDA) receptor in rat primary sensory neurons and its time course using whole-cell patch clamp technique. The majority of neurons (179/213, 84.0%) examined were sensitive to NMDA (0.1-1000 μM) with an inward current, and a proportion of the NMDA-sensitive neurons also responded to SP (78/98, 80.0%) with an inward current. Pretreatment with SP potentiated the NMDA-activated current (I NMDA) in a non-competitive manner, which is shown in that SP shifted the concentration-response curve for NMDA upwards compared with the control; the maximal value of INMDA increased fourfold, while the EC50 values for both curves were very close (28 vs. 30 μM). Furthermore, this potentiating effect was time-dependent: the amplitude of INMDA reached its maximum 20 min after SP preapplication, and thereafter maintained a steady level of about 2-3 times its control for 2 or even 3 h. This sustained potentiation by SP of INMDA could be blocked by extracellular application of WIN51708, a selective non-peptide antagonist of NK-1 receptor; and abolished by intracellular application of either BAPTA, or H-7, or KN-93. Though NMDA applied alone also induced a short-term (less than 20 min) self-potentiation of INMDA, it could be abolished by intracellular dialysis of BAPTA or KN-93 completely. As is known, the cell body of dorsal root ganglion (DRG) neurons is generally used as an accessible model for studying the characteristics of the membrane of primary afferent terminals in the dorsal horn of spinal cord. Therefore, these results may offer a clue to the explanation of the symptoms of chronic pain.

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