Lecture 6- NT Release Flashcards
Neurotransmitter release process pt. 1
- Vesicles are secured and docked, when the action potential reaches the terminal positive sodium ions enter the presynaptic terminal, making it more positive
- This depolarization allows a Ca2+ permeable channel (that sensors when the membrane is very positive) to open
- The Ca2+ will follow the conc. grad. and go into the cell
Neurotransmitter release process pt. 2
- Eventually enough Ca2+ in the cell will trigger proteins to move the vesicle and fuse it to the presynaptic neuron’s membrane
- Then the neurostransmitter is released into the synaptic cleft, opens a protein channel on the postsynaptic membrane and goes into the postsynaptic neuron
Calcium and neurotransmission
- Ca2+ is critical for release of neurotransmitters as it facilitates rapid fusion of synaptic vesicles to membrane (0.3-2ms)
- Neurotransmission can occur independent of Ca2+ but with much slower release
Neurotransmission- 2-way street?
- Dendrites can also release neurotransmitters
- Can release neurotrophic factors for growth, survival, and strengthening (plasticity)
- Can also release endocannabinoids (NT naturally produced and released by postsynaptic terminal)
What do autoreceptors do?
- Autoreceptors are a type of protein that reduce NT release by sending a signal to presynaptic to stop releasing a NT
Ionotropic receptors
- Receptors that are directly coupled with ion channels
- Receptors are activated by a NT binding to it, and opens almost like a channel so ions can flow through it
Metabotropic receptors
- Receptors are indirectly coupled and act via “messengers”
- NTs bind and a bunch of proteins (g-proteins) get released which can do a lot in the cell (change functions of things, can directly influence ionotropic receptors)
Neurotransmission ending
To terminate cell activity, NTs are deactivated by…
- Destruction or metabolism of neurotransmitters by enzymes (-“ase”) that exist in synaptic cleft so the signal can terminate
- Reuptake back up into the vesicles by transporters found on presynaptic terminals and glial cells
Basis for drug actions on neurotransmission:
- Drugs can affect the availability of the neurotransmitter in the synapse
- Drugs can affect receptors directly and can prevent or aid NT in doing their job (agonistic vs. antagonistic)
Anatagonist
A substance that stops the action or effect of another substance
Agonist
A substance that mimcs the actions of a NT or hormone to produce a response when it binds to a specific receptor in the brain
Tetrodotoxin
- Toxic chemical in puffer fish (fugu) that blocks sodium channels which prevents action potentials from occuring
- Used in research
Phenytoin (Dilantin)
- For epilepsy
- Decreases Na+ flow, slowing down action potential frequency and taking longer for an action potential to generate
Neurochemical Mechanisms of Drug Action
Synthesis
Agonist: increases
Antagonist: blocks the ability to synthesize
Neurochemical Mechanisms of Drug Action
Release
Agonist: promotes release
Antagonist: blocks/prevents ability to release
Neurochemical Mechanisms of Drug Action
Autoreceptors release
agonist: blocks release
antagonist: enhances release
Neurochemical Mechanisms of Drug Action
Post-Synatic receptors
Agonist: activates the receptors
Antagonist: blocks the receptors
Deactivation
Antagonist blocks reuptake or degradation
Classical NT
- Work in the classic way
- Includes glutamate, GABA, acetylcholine, dopamine, norepinephrine, epinephrine, serotonin
Non classical NT
- Don’t necessarily follow the one-way direction, can work backwards
- Includes anandamide, adenosine, histamine
Neurohormones
- Messenger that acts like a NT but is released in one place and acts somewhere else
- Includes CRF, oxytocin, vasopressin
Neuromodulators
- Any substance that alters neurotransmission in some way
- Neurotransmitteres would be a subset of neuromodulators
Acetylcholine
- One of the 1st NT discovered
- Resides outside of the brain to help muscles to contract, effects the neuromuscular junction and also functions from neuron to neuron. Invloved in some muscle disorders (ex. myasthenia gravis)
- Botox (Botulinum toxin) blocks acetylcholine so muscles cannot contract
Cholinergeric receptors
- Nicotinic- nicotine, agonist that mimics acetylcholine
- Muscarinic- atropine, antagonist that blocks receptors, is used to dilate pupils)
Alzheimer’s Disease
- Some deficit in CNS acetylcholine
- Atricept (donepezil) and Exelon (revastigmine) elevate acetylcholine levels by inhibiting acetylcholinesterase
