Lecture Nine

• Metabotropic Receptors:

  • G-protein coupled receptors (GPCRs) act as molecular switches
  • When bound as GTP, they are on; when bound as GDP, they are low energy and off
  • Act as second messengers
  • Neurotransmitter (NT) is the first messenger
  • G-proteins act in effector proteins, sending second messengers to open an ion channel
  • Slower than ionotropic receptors
  • G-protein coupled receptors have 7 transmembrane domains (TMD) (TM1-7)
  • G-proteins generally bind to the T5-T7 region but can also bind to T3 or T4
• Signal Amplification:

  • Provides extremely high sensitivity
  • One receptor can amplify many G-proteins, cyclic AMPs, and transfer phosphates to target proteins
• Characteristics of Metabotropic Receptors:

  • Slow
  • Slow post-synaptic potentials (PSPs)
  • Adenylyl cyclase can take milliseconds to catalyze the synthesis of single cAMP
  • Diffusible second messengers can take seconds to act (IP3)
  • Changes can last a lifetime (gene expression)
• • Presynaptic facilitation increases the amount of NT released by the presynaptic axon and increases the size of the PSP in the postsynaptic neuron
• Metabotropic Receptors Mediate Presynaptic Inhibition and Facilitation:

  • Presynaptic inhibition decreases the amount of neurotransmitter (NT) released by the presynaptic axon and decreases the size of the PSP in the postsynaptic neuron
  • Release of serotonin activates metabotropic receptors, which via cAMP, closes K+ channels, preventing repolarization and prolonging the action potential
  • Ca+ channels remain open for a longer period, increasing the amount of NT released and resulting in a longer PSP in the postsynaptic cell
• GABAA (ionotropic):

  • Release of GABA activates GABAA ionotropic receptors, opening Cl- ion channels
  • Cl- moves into the cell, decreasing the size of the action potential, reducing Ca+ entry, and the release of NT, resulting in a smaller PSP in the postsynaptic cell
• GABAB:

  • Release of GABA activates GABAB metabotropic receptors, which via cAMP, opens K+ channels
  • K+ efflux reduces the size of the action potential, leading to a decrease in Ca+ influx
  • The cAMP process can also inhibit Ca+ channels directly, decrease the release of NT, and result in a smaller PSP in the postsynaptic neuron