I know for fast EPSC non-NMDA channels are involved and similarly, slow EPSC is mediated by NMDA channels. But what's the actual mechanism underlying these processes?
The difference in kinetics of AMPA and NMDA channels is due to the difference in ... kinetics of the underlying ionic channels.
AMPA channels are chemical -gated ( by glutamate) channels that open very fast (
The difference in kinetics of AMPA and NMDA channels is due to the difference in ... kinetics of the underlying ionic channels.
AMPA channels are chemical -gated ( by glutamate) channels that open very fast (
Fabien’s answer is correct for AMPA glutamate channels. However, although the opening rate for NMDA channels is slower, they are also blocked by magnesium ions. This block is sensitive to the tansmembrane potential. So they are unblocked slowly at resting membrane potential, but they are less blocked and unblock more rapidly when the membrane potential is depolarized. The slowest glutamate EPSPs are the ones associated with metabotropic glutamate receptors, which are coupled to G-protiens.
Hi Linda,
You're sure right. Magnesium blockage is an another important property for NMDA channels to bear in mind.
Fabien
In terms actual mechanisms, the "off" or decay kinetics of EPSCs (currents measured in voltage clamp conditions) is determined by:
- Fast desensitisation in AMPA receptors (ms range)
- Slow dissociation of glutamate from its binding site in NMDARs (>100 ms)
The other important neurotransmitters that can generate fast and slow EPSPs are acetylcholine (nicotinic - fast; muscarinic-slow), serotonin (5-HT3-fast, slow = all the rest) and purinergic synapses (sorry, I cannot emunerate them correctly from memory).
The underlying mechanism for the typical slow deactivation of NMDARs is due to the presence of a unique intersubunit (N1-N2A) contact in their ligand binding domain. More specifically, a Tyrosine at position 535, was the culprit aa for the slower NMDA deactivation characteristic. Non-NMDA (AMPA, Kianate...) receptors lack (or may...) these stabilizing dimers and therfore deactivate faster. For more detail, see the paper from Popescu group in JBC (2015).
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