AMPA Receptor Study

Cody Clark, RN, BSN, SRNAYork College of Pennsylvania

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

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

Cellular Makeup• Tetrameric structure made of four subunits

• Each subunit an integral protein

Subunits

N-terminal domain

C-TailLu, W., & Roche, K. (2012). Posttranslational regulation of AMPA receptor trafficking and

function. Current Opinion In Neurobiology, 22(3), 470-479. doi:10.1016/j.conb. 2011.09.008

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

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

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

AMPA Along the Membrane

Magnesium Blockade

Calcium Influx

AMPA Upregulation

http://www.biopsychology.com/6e/step0402.html

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

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

Anesthesia Implications

• Diabetics

• Increased glucose levels cause an upregulation at GluA2

• Compensatory mechanism

• Tight glucose control

Anesthesia Implications

• Surgical pain hypersensitivity focused at Serine-831

• Intrathecal pretreatment?

https://faculty.washington.edu/chudler/spinal.html

Anesthesia Implications

• Calcium Channel Blockers?

• Nifedipine vs. P/Q and N type calcium channel blockers

• Cell Viability?

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), 913-

921.

Anesthesia Implications

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

Questions?

Thank You!!