neurotransmission

Study Guide: Neurotransmitters and Synaptic Transmission

1. What is a neurotransmitter?

A neurotransmitter is a chemical messenger that transmits signals across a synapse from one neuron to another, a muscle cell, or a gland. It bridges the communication gap between the presynaptic and postsynaptic cells, facilitating the transmission of electrical or chemical signals.



2. How are neurotransmitters released into the synapse?

  1. Action Potential Arrival: The action potential reaches the axon terminal.

  2. Voltage-Gated Calcium Channels: Depolarization opens voltage-gated calcium (Ca²⁺) channels, allowing calcium to enter the presynaptic terminal (axon terminal)

  3. Docking and Fusion: Synaptic vesicles containing neurotransmitters dock with the presynaptic membrane via SNARE proteins.

    • Small neurotransmitters 

      1. Predocked close to the presynaptic membrane for rapid release.

      2. Proteins change shape and vesicle membrane fuses with neuron membrane (both phospholipid bilayers) and release NTs

    • Neuropeptides dock further away and require prolonged calcium signaling for release.

  4. Exocytosis: Vesicles release neurotransmitters into the synaptic cleft through exocytosis.



3. How are neurotransmitters synthesized and stored?

  • Synthesis:

    • Small neurotransmitters (e.g., acetylcholine, GABA) are synthesized in the presynaptic terminal from precursor molecules using specific enzymes.

    • Neuropeptides are synthesized as larger precursors in the cell body and processed in the Golgi Apparatus and Rough ER during transport to the axon terminal

  • Storage:

    • Neurotransmitters are stored in synaptic vesicles in the axon terminal, ready for release.



4. What is the effect of neurotransmitter release on the postsynaptic membrane?

  • Neurotransmitters bind to receptors on the postsynaptic membrane, triggering two possible responses:

    • Excitatory Postsynaptic Potential (EPSP): Depolarization increases the likelihood of an action potential (e.g., Na⁺ influx).

    • Inhibitory Postsynaptic Potential (IPSP): Hyperpolarization decreases the likelihood of an action potential (e.g., Cl⁻ influx or K⁺ efflux).


                                     


5. What happens to neurotransmitters after binding to a receptor?

  1. Enzymatic Degradation: Neurotransmitters are broken down by specific enzymes (e.g., acetylcholine is degraded by acetylcholinesterase, neuropeptides = peptidase).

  2. Reuptake: Neurotransmitters are transported back into the presynaptic terminal via reuptake proteins for reuse (transporters specific to NT for small NTs)  

  3. Diffusion: Some neurotransmitters diffuse away from the synaptic cleft.



6. Conditions for a neurotransmitter as a chemical signal

A neurotransmitter must:

  1. Be synthesized and stored in the presynaptic neuron.

  2. Be released upon stimulation and act on a postsynaptic receptor.

  3. Be terminated by reuptake, degradation, or diffusion.

  4. When experimentally applied to a target, elicits the same response as in vivo.

Chemical Families of Neurotransmitters:

  • Amines: Dopamine, serotonin, norepinephrine.

  • Amino Acids: Glutamate, GABA, glycine, with Amine & R-group

  • Peptides: Substance P, endorphins, linking multiple AA’s

  • Catecholamines: with ring structure

  • Others: Acetylcholine, nitric oxide.




7. Voltage-Gated Calcium Channels and Neurotransmitter Release

  • The influx of calcium through voltage-gated channels is critical for neurotransmitter release.

  • High calcium levels trigger the SNARE complex to mediate vesicle fusion and release neurotransmitters into the synaptic cleft.

Small Neurotransmitters:

  • Released rapidly in response to low-frequency stimulation.

Neuropeptides:

  • Require higher or sustained calcium levels and are released during high-frequency stimulation.



8. Ionotropic vs. Metabotropic Receptors

  • Ionotropic Receptors:

    • Ligand-gated ion channels that directly alter membrane potential (e.g., NMDA receptor for glutamate).

    • Fast and short-lasting effects.

  • Metabotropic Receptors:

    • G-protein-coupled receptors (GPCRs) that initiate intracellular signaling cascades.

      • G protein swaps GDP for GTP when activated, changes shape to activate

    • Slower but longer-lasting effects.



9. Distinguish IPSP and EPSP Events

  • EPSP: Results from opening of Na⁺ or Ca²⁺ channels, causing depolarization.

    • Na+ or Ca2+ floods into cell (greater concentration outside of cell)

    • Cell MP becomes more positive

  • IPSP: Results from opening of Cl⁻ or K⁺ channels, causing hyperpolarization.

    • Cl- floods in or K+ floss out of cell (greater concentration inside cell)

    • Cell MP becomes more negative



10. Neurotransmitter Degradation and Reuptake

  • Degradation:

    • Acetylcholine → Broken down by acetylcholinesterase.

    • Peptides → Degraded by peptidases.

  • Reuptake:

    • Serotonin, dopamine, and norepinephrine → Reabsorbed by transport proteins (e.g., SERT, DAT, NET).