Synapses and neurotransmitters Flashcards
NMJ is
NMJ is a specialized synapse consisting of a presynaptic neuron (a motor neuron) and the sarcolemma (membrane of the muscle fiber).
Nt found at NMJ is
always ACETYLCHOLINE
Binding of ACh at sarcolemma causes
NMJ is a specialized synapse consisting of a presynaptic neuron (a motor neuron) and the sarcolemma (membrane of the muscle fiber).
Neurotransmitters are released at the synapse when ____________
when the intracellular Ca2+ reaches a certain level.
The increase in intracellular Ca2+ level is caused by Ca2+ influx which is a result of membrane depolarization
Name the major neurotransmitters in the CNS
Excitatory - 4
Inhibitory - 2
Both - 3
Excitatory
- Glutamate
- Epin
- Ne
- Substance P
Inhibitory
- GABA
- Opioids
Both
- Acetylcholine
- Serotonin
- Dopamine
Excitatory neurotransmitters cause _____1______ while inhibitory neurotransmitters ____2_______
- membrane depolarization
2. do not cause depolarization/cause hyperpolarization in the postsynaptic neurons.
Dopamine and serotonin can be excitatory or inhibitory depending on _______________
the subtypes of receptors that they bind to on the postsynaptic membrane.
Name the different types of neurotransmitters:
- ACh
- monoamines eg serotonin, ne, ep, dopamine, histamine
- Amino acids eg. Glutamate, glycine, GABA
- Purines eg. adenosine
- Gases eg. Nitric oxide
- peptides eg opioids
___________ is the most common excitatory neurotransmitter in the BRAIN.
Glutamate
Glutamate is synthesized in the neuron from glutamine. Glutamine is supplied by __________
the astrocytes nearby.
Glutamate
Two types of receptor: ionotropic and metabotropic. Explain them both
Ionotropic receptor mediates the effect of glutamate faster than metabotropic receptor as it is ion channel compared to metabotropic receptor which requires a second messenger system
It is conceivable that the ionotropic glutamate receptors are associated with cation channels since it is excitatory. Binding of glutamate to these receptors causes cation influx that will eventually lead to membrane depolarization.
Glutamate
Explain the types of ionotropic glutamate receptors, and their effect.
3 types of ionotropic glutamate receptors
- NMDA
- AMPA
- Kainate
All are fast and excitatory - Ca+ Na+ channels
Glutamate
Explain the types of Metabotropic (G protein coupled) glutamate receptors, and their effect.
3 types of metabotropic glutamate receptors
- group I - slow excitatory - mGlu1,5
- group II - slow inhibitory - mGlu2,3
- group III - slow inhibitory - mGlu4,6,7,8
Glutamate and its receptors play important role in _______ and _________
synaptic plasticity and excitotoxicity.
Excessive glutamate in the synaptic cleft can be caused due to _________.
due to dysfunction in the uptake mechanism or excessive release of glutamate from the neuron as a result of neuronal death.
Glutamate in the synaptic cleft continuously stimulate the postsynaptic neurons by binding to the glutamate receptor, leading to more neuronal death by excitotoxicity.
How is glutamate formed?
- Glutamate is absorbed by astrocyte
- converted to glutamine
- it is taken up by neuron
- converted to glutamate
GABA and glycine difference
GABA in brain
Glycine in spinal cord
__________ and __________ are the most common inhibitory neurotransmitters in the brain and spinal cord, respectively.
GABA and glycine
GABA is synthesized from _________
glutamate
using the enzyme Glutamate decarboxylase
GABA and glycine
Two types of receptor: ionotropic and metabotropic. Explain their speeds and
Ionotropic receptor mediates the effect of GABA and glycine faster than metabotropic receptor.
Ionotropic GABA receptors are associated with ________ since it is _________
anion channels since it is inhibitory.
Binding of glutamate to these receptors causes anion influx that will hyperpolarize the membrane, making it harder for the neuron to depolarize.
GABAA and GABAC receptors are associated with chloride channel. GABAB receptors, when activated, inhibits Ca2+ channels and opens K+ channels, resulting in hyperpolarization of the membrane.
What is the difference between ionotropic receptors of excitatory and inhibitory nt’s?
excitiatory - associated with CATION channels - causing depolarization
inhibitory - associated with ANION channels - causing hyperpolarization
Benzodiazepine binds to
Benzodiazepine binds to GABAA receptor to cause hyperpolarization in the neuron to produce its sedative effect.
What are the 3 main GABA channels?
- GABA-A : Cl- influx, IONOTROPIC
- GABA-B : Inhibit Ca2+, open K+. METABOTROPIC
- GABA-C : Cl- influx, IONOTROPIC
GABA-A and GABA-C receptors are associated with chloride channel, leading to hyperpolarization of neuron.
GABA-B receptors, when activated, results in hyperpolarization of the membrane.
Difference between ionotropic and metabotropic receptors?
Ionotropic:
faster, ligand/nt binds,
- for excitatory Ca2+ in, Na+ in
- for inhibitory Cl- in
Metabotropic:
slower, second messenger system (proteins/genes/ca affect ionotropic receptors)
GABA-A receptor has 6 binding sites for:
- barbiturates
- benzodiazepines
- GABA
- steroids
- picrotoxin
- chlorine
have similar effects if they bind to the same receptor
Acetylcholine is synthesized from
acetyl CoA and choline.
Acetylcholine is the only neurotransmitter released by the _______ and _________
preganglionic neuron at the ganglia
and
the only neurotransmitter released at the neuromuscular junction.
Acetylcholine has two types of receptor: ionotropic and metabotropic. what are they called specifically?
ionotropic = nicotinic
metabotropic = muscarinic
Acetylcholine
What are the different types of nicotinic and muscarinic receptors, and what are their effects?
Nicotinic - N1(NMJ) and N2(CNS) - EXCITATORY. (Associated with cation channels)
Muscarinic - M1,M2,M3,M4,M5 - EXCITATORY OR INHIBITORY
Serotonin is synthesized from
tryptophan
Serotonin has 2 types of receptors - ionotropic and metabotropic. Name them all and their effects.
General names: 5HT1 to 5HT7.
All metabotropic except for 3.
All excitatory except for 1 amd 5.
**inhibitory ones decrease cAMP in cell.
** To cause membrane depolarization, the intracellular cAMP level should increase and vice versa.
Which of the serotonin receptors are antidepressants and antiemetic?
Antiemetic - 3.
Antidepressants - 2,6,7.
Dopamine is synthesized from
L-tyrosine.
All of dopamine’s receptors are ____________.
metabotropic.
Dopamine can be excitatory or inhibitory.
D1-like receptor family (D1 and D5 receptors) are excitatory (G alpha S protein),
D2-like receptor family is inhibitory (G alpha i protein).
Dopamine is an important neurotransmitter in the
__________ and __________.
reward center (addiction) and for motor control (Parkinson’s disease).
In Parkinson’s disease, dopamine is low. Medication to increase it (increase synthesis, increase exocytosis) or maintaining (prevent breakdown or reuptake) the dopamine level
Serotonin syndrome - explain the mechanism
Due to increase in serotonin, causes over excitation.
Causes: SSRI + MAOI, cocaie, triptans, etc.
Signs/symptoms: mental status changes, autonomic instability - shes hot and wet!
Norepinephrine is synthesized from
dopamine.
All norepinephrine receptors are
metabotropic
What are the different types of receptors of norepinephrine?
alpha1,2 and beta1,2.
Except for α1 receptor which is linked to phospholipase C, the rest are linked to adenylyl cyclase.
Except for α2 receptor which is coupled to inhibitory G protein, the rest are coupled to stimulatory G proteins.
Except for β2 receptor which has higher affinity for ep>ne, the rest have the same affinity for both.
general rule for ne-receptors
1’s = alpha1 and beta 1= excitatory, cause more vasoconstriction, increased heart rate
2’s = inhibitory, cause muscle relaxation,
alpha’s present in blood vessels, and bronchioles
beta’s present in heart.
