Chemical signalling Flashcards
What happens when action potentials reach terminal bouton?
Open Ca2+ channels
What happens when Ca2+ channels open?
SNARE proteins activated; they cause docking of vesicles
What happens when vesicles dock?
Proteins cause tension in vesicular membrane; active system!
What ion (generally) does GABA affect?
Chloride
Comes into the cell and creates a negative charge
What are other names for direct-gated receptors?
fast-acting, ionotropic
What does a direct-gated receptor look like in terms of mechanism of action?
Neurotransmitter binds to transmembrane protein
Transmembrane protein opens, lets ions flow through
Do ionotropic or metabotropic receptors have a larger amplitude?
Metabotropic
Ionotropic only let ions flow through where they’re active; metabotropic causes large changes in the cell through second messengers
Which group of transmitters are generally associated with EPSPs/IPSPs (ionotropic)?
GABA, glutamate, acytylcholine
What is the ‘quanta’ of a transmitter?
The amount of transmitter within each vesicle
doesn’t vary wildly (e.g. 100 +- 5)
Hodgkin and huxley?
squid giant axons!
What are autoreceptors?
Receptors sensitive to transmitters.
Lets presynaptic cell know how much neurotransmitter is in the synapse
Found in the edges of synapses
If an agonist binds to an autoreceptor, what is the net effect?
antagonism: there’s ‘too much’ agonist in the synapse, so autoreceptor makes less get released
If a drug blocks an autoreceptor for agonists, what is the net effect?
Agonism.
Autoreceptor can’t send negative feedback to the presynaptic neuron when there’s too much agonist neurotransmitter in the synapse
What are the two major families of neurotransmitters?
Small molecule
Neuropeptide
What are the four families of small-molecule transmitters?
Acetylcholine, monoamines, amino acids, soluble gases
Synthesized in terminal or cell body (simple)
How is acetylcholine synthesized?
From choline by CHAT (choline acetyltransferase)
What are the main receptor types for acetylcholine?
Nicotinic (direct gating/ionotropic) > EPSPs
Muscarinic (indirect gating/metabotropic)
What kind of Ach receptors would you see in the neuromuscular junction?
Only nicotinic
What kinds of second messenger effects could you see from muscarinic receptors?
inhibition of cyclic AMP formation
Gets vague after that
What’s the synthetic pathway for the catecholamines?
Tyrosine >(tyrosine hydroxylase) > L-dopa >(dopa decarboxylase) > dopamine >(dopamine B-hydroxylase) > norepenephrine >(PNMT)> epinephrine
What neurotransmitters make up the monoamines?
Dopamine, norepenephrine, epinephrine (EPI) (all catecholamines)
Serotonin (indoleamine)
What kind of gating do the monamines have?
Indirect gating (metabotropic), all of them
What kind of neurotransmitter is serotonin?
an indoleamine
What neurotransmitters make up the amino acids?
Glutamate, GABA
What receptor type do the amino acids act on?
Both Indirect-gated (metabotropic) and direct-gated (ionotropic)
How are the amino acids inactivated?
Reuptake into neurons/glia
How is Ach broken down?
Only extracellularly, choline is taken back up
How many peptide neurotransmitters are there?
130+
How many peptide neurotransmitters use reuptake?
None.. they’re too big to bring back into the presynaptic neuron!
Means it’s really easy to get depleted
How hard is it for serotonin to get depleted?
REAL hard
What is the name of the thing a drug preventing storage of NT in vesicles would reduce?
quantal size
Is agonist/antagonist mean excitatory/inhibitory?
NO!! Depends on what is being antagonized/agonized
When might a peptide transmitter be released? What needs to be happening action potential-wise?
Peptides require more Ca2+ entry
Released when a neuron burst-fires, but not at low frequency
Neuromodulator
Chemicals without direct effect on postsynaptic cell - might e.g alter action of a standard neurotransmitter by changing its effectiveness
Active zone
Area on membrane neurotransmitter is released
Vesicles are primed and ready at active zones
Will neurotransmitters always be released if an action potential fires?
NO! Sometimes Ca2+ gets to terminal and nothing happens
Two different types of autoreceptors
Terminal autoreceptor - on axon terminals, inhibit further ntransmitter release
Somatodendritic autoreceptor - on cell body / dendrites, cause cell firing rate to slow
What’s different about autoreceptors / hetero?
Heteroreceptors: axoaxonic terminals, for receiving neurotransmitter from another neuron
What neurotransmitter is enzymatic breakdown important for?
Ach
What are transporters?
What neurotransmitters are relevent re: them?
Transport neurotransmitter back into cell membrane
Glutamate, GABA, monoamines
What drugs work by blocking neurotransmitter transporters?
Cocaine (blocks DA, 5-HT, NE)
Many antidepressants
When are ionotropic receptor subunits assembled?
Before insertion in the cell membrane
How many transmembrane domains do metabotropic receptors have?
7 (‘7-TM receptors’)
Metabotropic receptors for which neurotransmitters work by opening K+ channels for hyperpolarization?
Ach, DA, NE, 5-HT, GABA, neuropeptides (e.g endorphins)
What do effector enzymes do?
Make second-messengers do shit after being activated by a g-protein
