Notes

• Two different Neurotransmitter Receptor Types
  • Ionotropic (Ligand-Gated Ion Channels)
    • Short latency: rapid signals approx. 10ms.
    • Localization: usually postsynaptic.
    • Function: mediate fast synaptic transmission.
    • They change their conformation upon binding of the NT.
    • Typically 4/5 transmembrane domains
  • Metabotropic (GCPRs) (G-Protein Coupled Receptors)
    • Long latency: slow signals approx. 10sec.
    • Divergence: amplification of weak signals.
    • Convergence: integration of multiple inputs.
    • Localization: presynaptic and postsynaptic.
    • Function: modulate fast synaptic transmission.
    • Typically 7 transmembrane domains.
    • Three classes of GPCRs:
      • Class A (391 Olfactory)
      • Class B
      • Class C (GABAB)
    • The G-Protein has three subunits (alpha, beta, gamma).
    • It generates a cascade of events: NT arrives to receptors binds to G-protein the G-Protein subunits splits (GTP to GDP) Most of the work is done by the alpha subunit.
    • Divergent Roles for GPCRs: There are 3 main sequences of events:
      • cAMP System
      • Phosphoinositol System
      • Direct G Protein-Gating
    • Benefits of GPCRs
      • Amplification of the signal.
      • Modulation of cell function over a broad temporal range.
      • Diffusion of the signal to a large cellular volume.
      • Cross talk.
      • Coordination of diverse cell functions.

Glutamatergic-Excitatory

• Ionotropic Glutamate Receptors - AMPARs.
• Excitatory synapses depolarize the neuron.
• The generation of an EPSP: an impulse arriving in the presynaptic terminal causes the release of neurotransmitter. The molecules bind to transmitter-gated ion channels in the postsynaptic membrane. If Na+ enters the postsynaptic cell through the open channels, the membrane will become depolarized. The resulting change in the membrane potential (Vm), as recorded by a microelectrode in the cell, is the EPSP.
• Channels are very specific for certain ions, a small change in the gene code can block the passage of certain ions (e.g., Ca2+).
• Receptors are affected by drugs (e.g., PCP blocks NMDA receptors giving hallucinations).
• Protein complexes allow receptors to be presented and work as channels, but such protein complexes can be removed by the cell (plasticity).

GABAergic - Inhibitory

• Ionotropic receptor type topological arrangement - GABAARs.
• The Generation of an IPSP: an impulse arriving in the presynaptic terminal causes the release of neurotransmitter. The molecules bind to transmitter-gated ion channels in the postsynaptic membrane. If Cl- enters the postsynaptic cell through the open channels, the membrane will become hyperpolarized. The resulting change in membrane potential (Vm), as recorded by a microelectrode in the cell, is the IPSP.
• Several drugs to sleep better or relax are based on this concept, indeed these drugs target inhibitory receptors keeping them open for longer which allows more passage of Cl-, which in turn reduces the general spiking activity of the brain, thus inducing a sensation of relax which favors sleeping. Similar drugs are used also to cure Epilepsy.