Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate release of inhibitory amino acids in rat spinal cord dorsal horn

Local inhibition within the spinal cord dorsal horn is mediated by the neurotransmitters GABA and glycine and strongly influences nociceptive and temperature signaling. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are expressed by inhibitory interneurons and have been sh...

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Bibliographic Details
Published in:	Neuroscience Vol. 139; no. 2; pp. 539 - 553
Main Authors:	Engelman, H.S., Anderson, R.L., Daniele, C., MacDermott, A.B.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 2006 Elsevier
Subjects:	Age Factors alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology Animals Animals, Newborn Benzodiazepines - pharmacology Biological and medical sciences Cadmium Chloride - pharmacology Calcium - pharmacology Calcium Channel Blockers - pharmacology Dose-Response Relationship, Drug Drug Interactions Electric Stimulation - methods evoked release Fundamental and applied biological sciences. Psychology GABA gamma-Aminobutyric Acid - metabolism glycine Glycine - genetics In Vitro Techniques inhibitory synaptic transmission Kainic Acid - analogs & derivatives Kainic Acid - pharmacology miniature IPSCs Neural Inhibition - physiology Neural Inhibition - radiation effects NK1 receptor Patch-Clamp Techniques - methods Posterior Horn Cells - metabolism Rats Receptors, AMPA - agonists Receptors, AMPA - antagonists & inhibitors Receptors, AMPA - physiology Receptors, Presynaptic - physiology Spinal Cord - cytology Vertebrates: nervous system and sense organs mPSC AMPA NK1 receptor mIPSC inhibitory synaptic transmission APV mEPSC TASS TMR-SP evoked release eIPSC GAD65 eEPSC P TEA glycine GABA DRG NMDA TTX NK1R sIPSC miniature IPSCs Spinal cord NK1 Tachykinin receptor Rat Inhibitory postsynaptic current Rodentia Central nervous system Electrophysiology Glutamate receptor Posterior spinal horn Glycine Vertebrata AMPA receptor Mammalia Synaptic transmission Aminoacid Animal Neurotransmitter Release
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Summary:	Local inhibition within the spinal cord dorsal horn is mediated by the neurotransmitters GABA and glycine and strongly influences nociceptive and temperature signaling. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are expressed by inhibitory interneurons and have been shown to modulate GABA release in other regions of the CNS. In the spinal cord, there is morphological evidence for presynaptic AMPA receptor subunits in GABAergic dorsal horn neurons, but functional data are lacking. To determine if AMPA receptors are indeed functional at presynaptic terminals of inhibitory neurons, we recorded evoked and miniature inhibitory postsynaptic currents (mIPSPs) in the superficial dorsal horn of the rat spinal cord. We show that AMPA receptor activation enhances spontaneous release of inhibitory amino acids in the presence of tetrodotoxin onto both lamina II neurons and NK1 receptor-expressing (NK1R+) lamina I neurons. This effect is sensitive to the concentration of extracellular Ca 2+, yet is not fully blocked in most neurons in the presence of Cd 2+, suggesting possible Ca 2+ entry through AMPA receptors. Postsynaptic Ca 2+ elevation is not required for these changes. AMPA-induced increases in mIPSP frequency are also seen in more mature dorsal horn neurons, indicating that these receptors may play a role in nociceptive processing in the adult. In addition, we have observed AMPA-induced depression of evoked release of GABA and glycine onto lamina I NK1R+ neurons. Taken together these data support a role for presynaptic AMPA receptors in modulating release of GABA and glycine in the superficial dorsal horn. Because inhibition in the dorsal horn is important for controlling pain signaling, presynaptic AMPA receptors acting to modulate the inhibitory inputs onto dorsal horn neurons would be expected to impact upon pain signaling in the spinal cord dorsal horn.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2005.12.038