AMPA receptors transport

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. 

Wang Y, Small DL, Stanimirovic DB, Morley P, Durkin JP (1997) AMPA receptor-mediated regulation of a Gi-protein in cortical neurons. Nature 389 502 Wersinger E, Schwab Y, Sahel J-A, Rendon A, Pow DV, Picaud S, Roux MJ (2006) The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells. J Physiol (Lond) 577 221-34... 

Alanine-TR, [3-alanine transporter ALDH, aldehyde dehydrogenase ALDO-R, aldosterone receptor Aik Pase, alkaline phosphatase ALL-DB, alloxan-induced diabetic AMCV, artichoke mottled crinkle virus AMP, adenosine 5 -monophosphate 5 -AMP, adenosine 5 -monophosphate AMPA-R, AMPA-receptor AMPK, AMP-dependent protein kinase AMPKK, AMP-dependent protein kinase kinase... 

Another concept which complicates the interpretation of the roles of the transporters, is the idea of intersynaptic crosstalk. It has been suggested (Kullmann and Asztely, 1998) that the reason why larger quantal contents are sensed by NMDA receptors than by AMPA receptors is that glutamate is spilling over from one synapse to another. At the neighboring synapse, the concentration of glutamate is low. Because NMDA receptors have higher affinities than AMPA receptors, it follows that NMDA receptors will more readily be activated than the... 

AMPA receptors. This difference in quantal content is temperature-sensitive, being reduced at 37°C as compared to room temperature (Asztely et al., 1997). The authors suggest that the temperature effect could be due to glutamate transporters more efficiently preventing spillover at 37 C. This interpretation is strengthened by the finding that the temperature effect is sensitive to dihydrokainic acid, a glutamate uptake blocker. 

NMDA/AMPA/KA receptor activation evokes a rise in cytosolic Ca2+, activating a high capacity ruthenium red sensitive Ca2+ uniporter that transports Ca2+ into the mitochondria, which then activates mtNOS [338-340,442]. Activation ofnNOS/mtNOS,... 

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