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neurons communicate with one another by.....

releasing chemical messengers called neurotransmitters


main excitatory neurotransmitter



main inhibitory neurotransmitter



how to evoke synaptic response

binding to and activating neurotransmitter receptors, yielding any possible modes of synaptic signalling


after activating neurotransmitter receptors, neurotransmitter are removed from synaptic cleft by...

neurotransmitter transporters or degradative enzymes


3 different classes of neurotransmitters

1) classical (small molecule transmitters
- ACh, amino acids, biogenic amines derived from amino acids, purines

2) peptides
- endorphins etc.

3) non-classical, small molecule
- NO



- examples

- relatively large transmitter molecules (3-36 amino acids)

- endophrins, enkephalins, neuropeptide Y, vasoactive intestinal peptide, substance P, FMRDamide


small molecule transmitter

- individual amino acids (ex: glutamate, GABA)
and transmitters (ACh, serotonin, histamine)
- smaller than neuropeptides

- divided into: acetycholine, amino acids, purines, biogenic amines


what are biogenic amines

- examples
- subgroup

- small molecule transmitter (subgroup)

- similar chemical properties and postsynaptic actions
- examples: dopamine, norepinephrine, epinephrine, serotonin, histamine

- catcholamines (subgroup)


what are catcholamines?

- biogenic amine subgroup
- hydroxylated benzene ring


- basic processes to all chemical synapses (4)

- where is it made?

- synthesis
- package and release
- reception
- removal (simple slow diffusion)

- made in cytoplasm


synthesis of ACh

- precursors (2)
- enzyme
- transporter

- synthesized in nerve terminals, from precursors acetyl coenzyme A (kreb cycle) and choline

- enzyme: reaction catalyzed by choline acetyl transferase (ChAT or CAT)

- transporter: after synthesis in cytoplasm, vesicular ACh transporter loads ~10 000 molecules of ACh into cholinergic vesicle


how to determine the evolution of ACh?

(how do we know which tranmitter is used by which neuron for which function?)

- raise antibodies against ChAT (enzyme)
- knockout genes (synthesis of ChAT)
- any mutation of the enzyme is quickly lethal mutation


locations of ACh in vertebrate nervous system

- all motor neurons= spinal cord and brainstem
- autonomic nervous system (sympathetic and parasympathetic divisions)- fight or flight
- modulatory neurons in brainstem and basal forebrain- often involved with levels of activation (sleep/wake)- susceptible to Alzheimer's (boost ACh to relieve some symptoms)
- intrinsic neurons= basal ganglia, tectum


reception of ACh- 2 major types of receptors

1) nicotinic receptors
2) muscarinic receptors


nicotinic receptors

- example found..?
- iono/metabo
- conduct?
- made up of.. ?

- important for reception of ACh

- ex: found neuromuscular junction
- ionotropic
- conduct both Na and K (depolarizing- net flow of Na override outflow of K)

- composed of 5 subunits with 3-4 transmembrane domains which form a channel with central membrane-spanning pore
- ligand-gated channel - binding ACh, causes conformational change, rearranges receptor domains, opening gate, permittion ions to diffuse through pore


where does ACh bind on nicotinic ACh receptors?

on the alpha-subunit

(usually has 2 alpha subunits at neuromuscular junction )


muscarinic receptors

- example, found where?
- iono/metabo
- when do you want to use these?

- structure

- ex: targets of parasympathetic postganglionic neurones
- found on receptors of parasympathetic nervous system, heart muscles

- metabotropic receptor

- use ACh to speed up/slow down processes (ex: beating of heart)

- 7 transmembrane domains
- extracellular site to bind neurotransmitter
- intracellular site to bind G-protein
- activate inward rectifier K channels or Ca-activated-K channels, exerting inhibitory influence on dopamine-mediated motor effects


subtypes of muscarinic receptors

how does ACh bind?

M1, M2, M3, M4, M5
- different binding characteristics
- different reactions to drugs

- no subunits, each protein forms a complete receptor with its transmembrane domains


G-protein receptors
- iono/metabo
- how does it work
- 2 examples

- metabotopic receptor

- work indirectly to regulate activity in numerous other proteins including channels
- receptor lies within membrane, can mind to transmitter, has intercellular domain that can react to G-protein

- heterotrimeric or monomeric


2 differences between ionotropic and metabotropic receptors

1) speed (fast vs long lasting effects)
- fast= ionotropic
- slow= metabotropic

2) multiple actions


how any subtypes of muscrinic receptors are there?



removal of ACh

- post synaptic actions of ACh at many cholinergic synapses, is terminated by hydrolytic enzyme= acetylcholinesterase

- enzyme is concentrated in synaptic cleft, ensuring rapid decrease in ACh concentration after its release from presynaptic terminal

- choline produced by ACh hydrolysis, is RECYCLED by being transported back into nerve terminals, where it is used to re-synthesize ACh


Why is the process of chemical synapses of ACh important?

- differential effects of toxins and drugs-- pharmacology

- Agonists (drug mimics specific transmitter)
- antagonists (blocks transmitter)

- disease affecting cholinergic transmission


what is agonist and antagonist

- agonist= mimic endogenous ligand

antagonist= block endogenous ligand


example of nicotinic agonist

cholinergic substance

- nicotine binds to nicotinic receptors


nicotinic antagonist

- a-bungarotoxin from krait (used by snake, paralyze prey), prevents ACh from opening postsynaptic ion channels

- A-neurotoxin from cobra (blocks nicotinic receptor)

- curare (used as poison on darts to kill animals, blocks nicotinic receptors)


3 examples of muscarinic agonist and antagonist

- muscarine from the Amarita mushroom

- Summer flower

- Atropine from deadly nightshade (autumn berry)


effects of myasthenia gravis on neurotransmission and basis of treatment

- myasthenia gravis= disease that interferes with transmission between motor neurons and skeletal muscle fibers

- effects: autoimmune destruction of nicotinic receptors
- immunse responses reduced number of functional receptors at neuromuscular junction, eventualyl destroys them, diminishing efficiency of synaptic transmission

- muscle weakness occurs b/c motor neurons are less capable of exciting the postsynaptic muscle cells

- inhibitors increase concentration of ACh at synaptic cleft, allowing more effective activation of postsynaptic receptors not yet destroyed by immune system


each transmitter must always have mechanism for (4)

- synthesis
- package and release
- reception
- removal