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York College of Pennsylvania
AMPA Receptor Study Cody Clark, RN, BSN, SRNA York College of Pennsylvania
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Objectives Describe the cellular makeup of the AMPAR
Describe the most studied subunits of the AMPAR Describe the cellular functions of the AMPAR Describe the anesthesia implications found with the receptor
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What is the AMPA Receptor?
Alpha-amino-3-hydroxyl-5-methyl-4- isoxazolepropionic receptor (AMPAR) One of three Glutamate receptors found in the body Provides majority of excitatory transmissions in the body
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Cellular Makeup Tetrameric structure made of four subunits
Each subunit an integral protein Cellular Makeup N-terminal domain Subunits C-Tail Lu, W., & Roche, K. (2012). Posttranslational regulation of AMPA receptor trafficking and function. Current Opinion In Neurobiology, 22(3), doi: /j.conb
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GluA1 Subunit Most abundant subunit found within the AMPAR
Various sites of phosphorylation help to determine biophysical changes of the receptor Site S831compared to S567 TARPs, Protein 4.1N and various proteins interacting
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GluA2 Subunit Helps to determine permeability to Calcium
GRIP, ABP, and PICK1 proteins interacting with Site 880 SNARE type of protein named NSF helps to anchor AMPAR at membrane
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AMPA and NMDA? Activated AMPAR helps cause a depolarization
Helps to release a magnesium blockade in the NMDAR Influx of Calcium ions Phosphorylation of AMPAR subunits further
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AMPA Along the Membrane
Calcium Influx AMPA Upregulation Magnesium Blockade
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Long Term Plasticity and Depression
Signal transmission increased Extra connections made at synapses increasing signal of strength Leads to various functions in the body including memory, and acute/chronic pain
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Anesthesia Implications
Glucose control Acute and chronic pain a priority Have to prevent the formation of LTP Have to stop the upregulation of AMPA receptors within 3-6 hours to prevent consolidation
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Anesthesia Implications
Diabetics Increased glucose levels cause an upregulation at GluA2 Compensatory mechanism Tight glucose control
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Anesthesia Implications
Surgical pain hypersensitivity focused at Serine-831 Intrathecal pretreatment?
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Anesthesia Implications
Calcium Channel Blockers? Nifedipine vs. P/Q and N type calcium channel blockers Cell Viability?
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Joshi, D. C. , Singh, M. , Krishnamurthy, K. , Joshi, P. G
Joshi, D. C., Singh, M., Krishnamurthy, K., Joshi, P. G., & Joshi, N. B. (2011). AMPA induced Ca2+ influx in motor neurons occurs through voltage gated Ca2+ channel and Ca2+ permeable AMPA receptor. Neurochemistry International, 59(6),
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Anesthesia Implications
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Take Home Messages AMPA receptor is an integral protein that is slowly being realized with the importance it holds in the formation of chronic pain pathways and formation of certain memory pathways AMPA is vital in the activation of the NMDA receptor and further activation of pain and memory impulses AMPAR is connected with glucose control, surgical incision pain, and formation of LTP Medications, including Calcium channel blockers are being investigated for the effects they can ultimately have on the AMPAR and its functions
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Questions?
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Thank You!!
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