AMPA receptors spinal cord

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

Cheng, G. and Kendig, J. J. Enflurane directly depresses glutamate, AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAa or glycine receptors, Anesthesiology 2000, 93, 1075-1084. 

Recently, it has been shown that spinal neurons express functional kainate receptors which contribute to synaptic transmission between primary afferent fibers and dorsal horn neurons (Li et al., 1999). Administration of the AMPA/kainate antagonist CNQX to the spinal cord... 

Furuyama, T., Kiyama, H., Sato, K., Park, H.T., Maeno, H., Takagi, H., Tohyama, M. Region-specific expression of subunits of ionotropic glutamate receptors (AMPA-type, KA-type, and NMDA receptors) in the rat spinal cord with special reference to nociception, Brain Res. Mol. Brain Res. 1993, 18, 141-151. 

Procter, M. J., Houghton, A.K., Faber, E.S., Chizh, B.A., Omstein, P.L., Lodge, D., Headley, P.M. Actions of kainate and AMPA selective glutamate receptor ligands on nociceptive processing in the spinal cord, Neuropharmacology 1998, 37, 1287-1297. 

Sun H., Kawahara Y., Ito K., Kanazawa I., and Kwak S. (2005). Expression profile of AMPA receptor subunit mRNA in single adult rat brain and spinal cord neurons in situ. Neurosci. Res. 52 228-234. 

Topiramate blocks repetitive firing of cultured spinal cord neurons, as do phenytoin and carbamazepine. Its mechanism of action, therefore, is likely to involve blocking of voltage-dependent sodium channels. Topiramate also appears to potentiate the inhibitory effect of GABA, acting at a site different from the benzodiazepine or barbiturate sites. Topiramate also depresses the excitatory action of kainate on AMPA receptors. It is possible that all three of these actions contribute to topiramate s anticonvulsant effect. 

Engelman HS, Anderson RL, Daniele C, MacDermott AB (2006) Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate release of inhibitory amino acids in rat spinal cord dorsal horn. Neuroscience 139 539 Engelman HS, MacDermott AB (2004) Presynaptic ionotropic receptors and control of transmitter release. Nat Rev Neurosci 5 135 45... 

Ruiz A, Fabian-Fine R, Scott R, Walker MC, Rusakov DA, Kullmann DM (2003) GABAA Receptors at hippocampal mossy fibers. Neuron 39 961 Rusakov DA, Saitow F, Lehre KP, Konishi S (2005) Modulation of presynaptic Ca2+ entry by AMPA receptors at individual GABAergic synapses in the cerebellum. J Neurosci 25 4930-40 Rustioni A (2005) Modulation of sensory input to the spinal cord by presynaptic ionotropic glutamate receptors. Arch Ital Biol 143 103-12... 

AMPA RECEPTOR SUBUNIT mRNAs IN THE LUMBAR SPINAL CORD... 

Fig. 21. (a-b) The expression of the AMPA receptor subunit genes (GluR-A, GluR-B, GluR-C and GluR-D) in the adult rat lumbar spinal cord (X-ray film autoradiographs, coronal sections). Scale bar, 3(X) pm. (Tolle et al., 1993). 

Visceromotor neurons in the rat lumbosacral (L6-S1) spinal cord express different AMPA receptor subunit mRNAs from ventral horn motor neurons, namely GluR-A and -B, with little or no GluR-C or -D mRNAs (Shibata et al., 1999). Visceromotor neurons also differ from ventral horn motor neurons in their NMDA receptor subunit gene expression (Shibata et al., 1999 see above). 

Kainate receptor subunit mRNAs are not abundant in the adult spinal cord, and GluR6 is not expressed at all (Tdlle et al., 1993). In the dorsal horn, occasional cells express the GluR5 and GluR7 subunit genes, and more cells contain KA2 mRNA (Tolle et al., 1993). Kainate receptors are probably in subsets of AMPA receptor-positive cells. Most of the GluRS protein in the dorsal horn is on the primary afferent terminals of DRG cells (Woolf and Costigan, 1999). 

Engelman HS, Allen TB, MacDermott AB (1999) The distribution of neurons expressing Ca +-permeable AMPA receptors in the superficial laminae of the spinal cord dorsal horn. J Neurosci 79 2081-2089. 

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