neurotransmitters Flashcards
what is a classical neurotransmitter?
synaptic transmission from pre- to postsynaptic neuron
what is an auto neurotransmitter?
neurotransmitters act on pre-synaptic neuron (themselves)
acts on the same cell (or nearby cells) that released it
what is a retrograde neurotransmitter?
synaptic transmission from post to pre-synaptic cell (e.g cannabinoid)
how does a neurotransmitter act?
- direct effect on membrane potential – EXCITATORY and
INHIBITORY - indirect effect on membrane potential – positively or negatively MODULATORY
- indirect effect on transmitter release – generally negatively
MODULATORY
direct effect on membrane requires…
ion channels as they need to change the membrane potention
change in potentials in dendrites lead to…
EPSP (excitatory postsynaptic potential) or IPSP (inhibitory postsynaptic potential)
are EPSPs all or nothing?
no, they depend on ion influx amount
receptors activated by neurotransmitters rather than voltage
ligand gated ion channels on centre of synapse
metabotropic receptors (postsynaptic)
on outside of synapse
work via second messenger model (protein G)
modulate effectiveness of ligand gated ion channel e.g switch off when too much stimulation or positively modulatory of they are not activated efficiently
pre-synaptic autoreceptors and neurotransmitters
acting on own receptors
almost always negatively modulatory (auto neurotransmitters inhibit the further release of neurotransmitters from the presynaptic neuron)
why are almost all pre-synaptic auto-neurotransmitters negatively modulatory?
break in transmission (go, stop, go, stop) to separate each incoming signal
negative feedback via autoreceptors on the presynaptic neuron serves as a built-in mechanism to limit the amount of neurotransmitter released
what two types of neurotransmitters are constantly acting at the same time?
classical and auto
what are the classes of neurotransmitter?
- amino acids
- acetylcholine
- monoamines
- adenosine and ATP
amino acid structure
amine group, carboxyl group, variable R group and hydrogen
neurotransmitters co-opted from roles in protein structure and function
what are the most common amino acid neurotransmitters?
L-glutamate
glycine
γ-aminobutyric acid (GABA) (has amino and carboxyl group but not technically AA)
what is the smallest amino acid?
glycine
what is GABA made from?
glutamate
L-glutamate class
major EXCITATORY neurotransmitter in the CNS
acts at post-synaptic receptors (binds to glutamate receptors on the postsynaptic neuron leading to depolarisation)
some evidence for pre-synaptic receptors
GABA class
major INHIBITORY neurotransmitter
acts at pre- and post-synaptic receptors
released from a presynaptic neuron into the synapse, it binds to GABA receptors on the postsynaptic neuron, typically causing hyperpolarization
glycine class
INHIBITORY neurotransmitter in spinal cord and brain stem (main)
EXCITATORY co-agonist at glutamatergic
NMDA receptors (bind and allow calcium ions)
typically leads to the opening of chloride (Cl-) channels, allowing chloride ions to flow into the postsynaptic neuron, causing hyperpolarisation
other more unusual amino-acids can also
bind to the glycine site (ligand gated ion channel) e.g. D-serine
what receptors do inhibitory neurotransmitters act on?
anion channels (negatively charged ions across membrane)
what receptors do excitatory neurotransmitters act on?
cation channels (positively charged ions across membrane)
how does the stretch reflex work in terms of EPSP and IPSP systems?
synapse between EPSP and IPSP makes sure EPSP fires first to allow stretch and relax of muscle after
what is the effect of gabazine on GABA?
no effect (continued EPSP and IPSP)
what is the effect of strychnine on gylcine?
by antagonizing glycine receptors, strychnine prevents chloride ion influx and inhibits the inhibitory effects of glycine
only EPSP activates so no relxation of muscle
what does strychnine do to the body?
poisoning causes uncontrolled muscle contraction
by inhibiting glycine receptors in the spinal cord
acetylcholine class
EXCITATORY transmitter at the
neuromuscular junction (NMJ)
and autonomic nervous system
widespread in the CNS
forms a diffuse MODULATORY system throughout the basal
forebrain and brain stem
what is the function of acetylcholine?
modulation of arousal, sleepwake cycles and memory formation
what are cholinergic systems and diffuse modulatory networks important for?
modulates other neurotransmitters
alzheimers and acetylcholine
cholinergic diffuse modulatory network often first system to break down in patients with alzheimers
types of monoamines
catecholamines (L-phe and L-Tyr) e.g dopamine, adrenaline (epinephrine) and noradrenaline (norepinephrine)
tryptamines (L-Trp) e.g serotonin
what are monoamines?
a large group of neurotransmitters derived from the aromatic amino-acids (
L-Phenylalanine, L-Tyrosine and L-Tryptophan)
they have a single amine group
role of monoamine neurotransmitters
form diffuse MODULATORY networks throughout the cortex and brain stem
c.f. acetylcholine
overlapping functions based around mood, emotion, appetites and
attention
histamines (monoamines)
produced from the amino-acid histidine
usually associated with hayfever and inflammation
role of histamine as a neurotransmitters
histamine acting via H1
receptors is a positive modulator throughout the brain
histaminergic neurons in the
tuberomamillary nucleus act as
pacemakers (mamillary bodies)
firing rate drops during sleep
how does histamine regulate the sleep-wake cycle?
histamine acts via presynaptic H3
receptors to negatively modulate other synapses (monoamines, GABA, glutamate)= heteroreceptors
ATP
act via EXCITATORY P2X receptors and
both +ve and –ve MODULATORY
P2Y/P1 receptors
important in neuron-glial cell interactions
roles in axon guidance,
neurogenesis and developmena
why do classical and auto neurotransmitters act simultaneously?
classical and auto neurotransmitters work together to maintain the balance of synaptic transmission
while classical neurotransmitters drive signal transmission (excitation or inhibition), auto neurotransmitters act to modulate the strength of that transmission
adenosine
act via negative modulatory A1-A3 receptors across the brain and cardiovascular system
what is positive modulation?
positive modulation refers to the process by which a molecule increases the activity of a receptor or ion channel
what is negative modulation?
negative modulation refers to the process by which a molecule decreases or inhibits the activity of a receptor or ion channel
