Question

Compare the function and regulation of activity of NMDA and AMPA
receptors and their importance in the induction of long term
potentiation (LTP).

Answer 1

1.) AMPA and kainate channels are similar to ACh channels in the sense that when glutamate binds to these receptors, both Na+ and K+ currents flow quickly through the same pore. When glutamate binds to AMPA and Kainate receptors, channels open and allow Na+ and K+ to flow through, depolarization occurs. These channels can be blocked by CNQX.
2.) NMDA channel: This channel requires glutamate, approximately 30 mV of depolarization, and presence of glycine to open and conduct current. NMDA channel is plugged by Mg++, 30 mV of depolarization unplugs the channel. Once open, this channel allows Ca++, Na+ and K+ to flow through. NMDA channel can be blocked by the drug APV.
3.) Here is how the two types of channels are related. When glutamate is released, it binds to various types of glu tamate gated channels. The initial currents flows through AMPA channels, which generate depolarization. When this depolarization reaches 30 mV, NMDA channels get unplugged (Mg++ out), Ca++, Na+ and K+ currents flow through NMDA pores. The currents through NMDA channels are late currents

4.) Both receptors activate their respective ion channels upon binding of transmitters.

   NMDA channels have a magnesium ion at their core, AMPA channels do not.Upon binding of transmitters on AMPA receptors, sodium enters the AMPA channels and depolarisation occurs.Only when a certain level of depolarisation is reached will the magnesium ion in the NMDA channels be dislodged.
   At this point, calcium and sodium will enter the NMDA channels. The influx of calcium inside the cells activates protein kinases and this plays a part in long-term potentiation.
5.) Main points:
   NMDA channels have a magnesium ion at their core, unlike AMPA channels.Calcium influx occurs (in addition to sodium influx) in NMDA channels while only sodium influx occurs in AMPA channels.

6.) We may still not have the complete picture but we are confident enough that these parts have been thoroughly investigated:
   a.)AMPA receptors are the first post-synaptic receptors to be activated.
b.)Depending on the frequency of the stimulation, the activity of the AMPA receptors (AMPA-R) may allow, in the case of LTP (or may not allow, in the case of LTD) the persistent activation of the NMDA receptors (NMDA-R), by causing the removal of the Mg++ ions, up to that point hindering their function.
7.) As the events of the synaptic modification progress, AMPA-R may also contribute to the activation of the Voltage-dependent Calcium channels (VDCCs) which have been linked to the electrostructural alterations required for a functional synaptic plasticity - which include the organized insertion of more NMDA-R at the post-synaptic density area.