Lecture Eight

• Ligand-gated ion channels are fast channels involved in signal transmission
• Ionotropic receptors are ligand-gated ion channels, as opposed to voltage-gated ion channels
• Ligand-gated ion channels are not necessarily cation-specific, for example, the acetylcholine nicotinic receptor is permeable to K+ and Na+
• All ligand-gated ionotropic receptors are similar, consisting of 5 subunits, each with 4 transmembrane segments, two of which are binding segments
• Ionotropic receptors have a common ancestry, with the exception of Glutamate having 4 subunits, each with 3 transmembrane segments (M1, M3, M4), and M2 as a reentrant pore loop
• Each subunit of Glutamate ionotropic receptors has a binding site on the N-terminal tale and extracellular loop between M3 and M4, and the channel opens when two binding sites are occupied
• • NMDA receptors: typically heterotetramers with 3 GluN1 and 2 GluN2 subunits, having 2 glutamate (GluN2) and 2 glycine (GluN1) binding sites, being permeable to K+, Na+, and Ca+, and partially voltage-dependent
• Main types of Glutamate ionotropic receptors include:

  • AMPA receptors: most common, usually heterotetrameric dimers with 4 subunits, not all the same, with two identical subunits, such as GluA2-GluA1 complexes
  • Kainate receptors: with 5 receptor subunits (GluK1-5) assembling as heterotetramers or homotetramers, allowing Na+ and K+ to pass freely with low permeability for Ca+, resulting in slower EPSP compared to AMPA receptors
• Zinc ions, proteins, and polyamines also have binding sites on NMDA receptors
• Kainate receptors consist of 5 receptor subunits (GluK1-5) that assemble as heterotetramers or homotetramers
• These receptors allow Na+ and K+ to pass freely, but have low permeability for Ca+
• Kainate receptors produce slower excitatory postsynaptic potentials (EPSP) compared to AMPA receptors