Lecture 14_LGICs Flashcards
What are neurotransmitters?
Small molecules released by neurons that bind to receptors and elicit functional effects.
What two things can happen after neurotransmitters bind to receptors?
- EPSP: Increase the likelihood of action potential generation in the postsynaptic cell (increase membrane potential, makes it more positive).
- IPSP: Decrease the likelihood of action potential generation (may decrease membrane potential).
The nature of a postsynaptic cell’s response to neurotransmitters depends on:
- The type of neurotransmitter released
- The type of receptor(s) on the postsynaptic cell
- The magnitude of the response to neurotransmitter
The magnitude of response to neurotransmitter depends on:
- Quantity of neurotransmitter released
- Receptor numbers
- State of the receptors (are they able to respond to neurotransmitter)
Two major categories of neurotransmitter receptors:
- Ionotropic: Neurotransmitter binding causes a conformational change in the receptor which leads to the rapid opening of the pore in the receptor, permitting ions to flow down their electrochemical gradients.
- Metabotropic: Neurotransmitter binding causes a conformational change in the receptor which leads to a second messenger cascade (i.e. through G-protein activation). These responses are of slow onset and long duration, compared to ionotropic receptors.
Ions can’t go between lipids (because of their extremely low Pm/b values), so…
…receptors function as pores for these low Pm/b molecules to go through.
General characteristics of ionotropic receptors:
- Multi-subunit protein complexes with membrane-spanning domains.
- Very fast onset (sub ms time scale)
- Ion selectivity (cation vs anion selectivity)
- Most desensitize rapidly after exposure to agonist.
This desensitization only lasts for a short period, then channel re opens.
(T/F) Ions interact with specific amino acids of pores and are dehydrated during pore passage.
TRUE. The pore is so small that the ions have to be dehydrated.
ACh receptor has two binding sites for ACh. What does this mean?
It takes two ACh molecules to bind to ACh receptor (cooperativity of binding between the two site sis evident).
If you only have a few kind of transmitters, how do you maintain diversity?
- It depends on the receptor subunits and the combination of them (no such thing as a GABA receptor or ACh receptor).
- You test the homology of a new subunit, and see which type of subunit it resembles the most.
Consequence of agonist binding to a neurotransmitter receptor
- Closing and opening events of ligand gated channel, followed by a long stretch of closing is the desensitized state.
- Over time, if agonist is kept unbound, the channel will resensitize and allow flow of ions through.
- This is a random, memory-less process.
Unitary conductance:
Reflection of how many ions are coming through per unit of time.
What are the major inhibitory neurotransmitters in the brain and spinal cord? How can you upset the balance of the nervous system with these?
- GABAR and GlyR are the major inhibitory neurotransmitters in the brain and spinal cord (conduct Cl- ions).
- Inhibition of GABA or Gly receptors cause convulsions (picrotoxin).
- Enhancement of GABA or Gly receptor function would lead to sedation and anesthesia (alcohol and volatile anesthetics).
Give an example of a clinically useful allosteric modulator having an effect on receptor function.
BZ is responsible for sedative effect of benzodiazepines (enhancing function of GABA receptors).
Describe Benzodiazepines
- It is an allosteric modulator (modulates effect of GABA).
- Examples are dizepam (valium), flunitrazepam (rohypnol), and chlordiazepoxide (librium).
- Benzodiazepines shift GABA dose concentration curve to the left, and have no effect in absence of GABA.
