Stimulation of α1-adrenoceptors reduces glutamatergic synaptic input from primary afferents through GABAA receptors and T-type Ca2+ channels

W. X. Yuan, Shao-Rui Chen, H. Chen, Hui-Lin Pan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Activation of the descending noradrenergic system inhibits nociceptive transmission in the spinal cord. Although both α1- and α2-adrenoceptors in the spinal cord are involved in the modulation of nociceptive transmission, it is not clear how α1-adrenoceptors regulate excitatory and inhibitory synaptic transmission at the spinal level. In this study, inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs, respectively) were recorded from lamina II neurons in rat spinal cord slices. The specific α1-adrenoceptor agonist phenylephrine significantly increased the frequency of GABAergic spontaneous IPSCs in a concentration dependent manner, and this effect was abolished by the α1-adrenoceptor antagonist 2-(2,6-dimethoxyphenoxy)ethylaminomethyl-1,4-benzodioxane (WB4101). Phenylephrine also significantly reduced the amplitude of monosynaptic and polysynaptic EPSCs evoked from primary afferents. The inhibitory effect of phenylephrine on evoked monosynaptic glutamatergic EPSCs was largely blocked by the GABAA receptor antagonist picrotoxin and, to a lesser extent, by the GABAB receptor antagonist CGP55845. Furthermore, blocking T-type Ca2+ channels with amiloride or mibefradil diminished the inhibitory effect produced by phenylephrine or the GABAA receptor agonist muscimol on monosynaptic EPSCs evoked from primary afferents. Collectively, these findings suggest that activation of α1-adrenoceptors in the spinal cord increases synaptic GABA release, which attenuates glutamatergic input from primary afferents mainly through GABAA receptors and T-type Ca2+ channels. This mechanism of presynaptic inhibition in the spinal cord may be involved in the regulation of nociception by the descending noradrenergic system.

Original languageEnglish (US)
Pages (from-to)1616-1624
Number of pages9
JournalNeuroscience
Volume158
Issue number4
DOIs
StatePublished - Feb 18 2009

Fingerprint

GABA-A Receptors
Adrenergic Receptors
Phenylephrine
Spinal Cord
Mibefradil
Substantia Gelatinosa
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Picrotoxin
Inhibitory Postsynaptic Potentials
Muscimol
Nociception
Amiloride
Excitatory Postsynaptic Potentials
Synaptic Transmission
gamma-Aminobutyric Acid
Neurons

Keywords

  • GABA receptors
  • GABA receptors
  • descending noradrenergic modulation
  • presynaptic inhibition
  • spinal cord
  • α-adrenoceptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Stimulation of α1-adrenoceptors reduces glutamatergic synaptic input from primary afferents through GABAA receptors and T-type Ca2+ channels. / Yuan, W. X.; Chen, Shao-Rui; Chen, H.; Pan, Hui-Lin.

In: Neuroscience, Vol. 158, No. 4, 18.02.2009, p. 1616-1624.

Research output: Contribution to journalArticle

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