Neurochemistry 1 Flashcards by Michelle Doody

Name the different types of glial cells

Which are the most abundant

Astrocytes
Oligodendrocytes
Schwann cells
Microglia

Astrocytes are the most abundant

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Function of microglia

Immune cells

Secrete cytokines - when they become activated this increased inflammatory cytokines and cause inflammation

this is seen a lot of people with neuro degenerative diseases

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Define synapse

Specialised sites where neurons communicate with other cells via NTs

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Name the 4 steps in neurotransmission

NT synthesised and stored in high conc in nerve terminals, in synaptic vesicles
Released upon stimulation of nerves
Stimulates target organs/cells
Active mechanisms to terminate its effect

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Name the 3 classifications of NTs

GIve examples

Classical (small molecule) NTs

Neuropeptides (non-classical NTs) - short peptides (3-36 AAs long) that are neuroactive

Unconventional - NO (cannot be stored in nerve terminal), CO (cannot be stored in nerve terminal), arachidonic acid (not easily stored in nerve terminal)

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Name the 3 small molecule NTs that are derived from tyrosine

Dopamine

Norepinephrine

Epinephrine

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As a general rule, what do classical NTs have in common

Either AAs or derived from AAs (except ACh)

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What is serotonin derived from

What is its synonym

Tryptophan

5-hydroxytryptamine

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What is histamine derived from

Histidine

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What is GABA derived from

Name its synonym

What is unique about GABA

Derived from glutamate

γ-aminobutyric acid

Non-typical but still has an amino grp and a carboxylic acid grp

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What do ACh, glycine and glutamate have in common

All classical (small molecule) NTs

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In step 1 of neurotransmission, synthesis and storage of NT in high conc in nerve terminals, where does the synthesis usually occur

Cytosol

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How is NT transported into synaptic vesicles

Dependent on 2 proteins:

H+-ATPase (proton) pump - creates H+ gradient (by pumping H+ INTO vesicle) across vesicle membrane, pumping
H+/NT antiporter - uses the energy stored in this H+ gradient so H+ leaves and a NT enters

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What is step 2 in neurotransmission

Release of NT upon stimulation of the neuron

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How is NT released

Exocytosis of synaptic vesicles is tightly coupled to arrival of an AP at the axon terminus

Also dependent on Ca2+ influx into the presynaptic nerve terminal

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Define AP

What is its speed

Electrical signal that travels from neuronal cell body down the axon to the axon terminus

Characterised by high speed (up to 120 m/s) with no loss of signal over long distances

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What structures wrap around the axon

Oligodendrocytes/Schwann cells

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What is the composition of myelin

70-80% lipid

20-30% protein

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Role of Ca2+ in NT release

This electrical signal must be converted into a chemical signal - Ca2+

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As a result of the opening of the VG Ca2+ channels, how does [Ca2+] change

80-100 nM → 1-100 uM

Increase in Ca2+ is highly localised

How is a low Ca2+ conc maintained in the axon

Ca2+ pumps pump Ca2+ back out to maintain low conc in cytosol

Mitochondria also have a Ca2+ uptake system

Name 2 SNARE proteins

SNAP25 and Synaptobrevin

Function of Synaptotagmin

Ca2+ sensing

Function of Synapsin

Links proteins to cytoskeleton and keeps vesicles in place

What does the V-ATPase do

Pumps H+ into cell

Name the SNARE protein present on the VESICULAR membrane

Synaptobrevin

Name the SNARE protein present on the plasma membrane

Syntaxin

Name the SNARE protein present on both membranes

SNAP-25

Function of SNARE proteins

Control fusion of 2 membranes

Describe the structure of synaptotagmin

Made up of long alpha helices - bind and become intertwined with each other - stable complex, that is highly resistant to degradation

What does the SNARE complex look like

MOA of action of synaptotagmin

Affinity for Ca2+ = 1uM Binding of Ca2+ to synaptotagmin changes its confirmation and it pulls the vesicle closer to the mebrane this then stimulates the fusion of the 2 membranes and NT is exocytosed into the synaptic cleft

What diseases affect the presynaptic terminal - give an example What are the symptoms What is it caused by

Some myasthenic syndromes e.g. the autoimmune disease Lambert-Eaton myasthenic syndrome (LEMS) - attacks presynaptic Ca2+ channels Present as muscle weakenss that worsens with exertion Caused by abnormal transmission at neuromuscular synapses ALSO clostridium bacterial toxins (even if you stimulate this neuron it cannot change the voltage)

Describe the vesicle cycle

Loaded with NT Move into reserve pool Linked via synapsin to cytoskeleton AP arrives they become mobilised to nerve terminal pre-synaptic membrane Docked onto membrane and primed Linkages to membrane are shown Ca2+ influxes into cell and then get fusion with the plasma membrane and exocytosis of its contents The membrane that was part of the vesicle gets re-taken up - clatherin coating Empty vesicle then gets reloaded with NT

Where does botulinum toxin come from Describe its structure

From clostridium botulinum, which causes food poisoning and paralysis Heavy chain involved in entry into neurons in NMJ Light chain has protease activity

Why does BOTOX have an effect on muscles

Attracted to neurons at the neuromuscular junction

Distinguish between the heavy and light chain in botulinum toxin

Heavy chain - involved in entry into neurons in the NMJ Light chain - protease activity

How can toxins affect transmitter release

Because the light chain has protease activity, it degrades the snare proteins and the snare complex cannot form =\> vesicle will not be able to fuse with the plasma membrane and there will be no NT release Nerve terminals can grow new ones but takes months

Medical uses of Botox

Strabismus (crossed eyes) Blepharospasm (uncontrolled blinking) Hyperhidrosis (excessive sweating) Glabellar frown lines Chronic migraines

What is step 3 in neurotransmission

When it is released into the synaptic cleft, the NT binds and activates receptors on the post-synaptic cell membrane

Name the 2 types of NT receptors

Ionotropic - ligand gated ion channel Metapotropic - GPCR

What receptors do classical NTs bind to

Both to specific ionotropic and metabotropic receptors

What is the defining feature of ionotropic receptors

Generally heteromeric - individual receptors are made of multiple subunits

Name the glutamate receptors

Overview of subunits for the different types of receptors

MOA of heteromeric ion channels

NT are binding to 1 or 2 of these subunits - we notice that certain subunits have a higher affinity of binding than others Change the conformation and opens channel in the interior pore formed by the 5 subunits This allows flux of certain ions Signal is transduced into post-synaptic cell

Describe metabotropic receptors Give examples What sort of response do they elicit

7 transmembrane domain e.g. Adenylate cyclase, phospholipase C or A, ion channels Responses tend to be slower than for ionotropic receptors and of longer duration

What are the different receptor classes and their receptor subtypes

Step 4 in neurotransmission

Termination of the effect of the NT

Name the main mechanisms for termination response

1. Enzymatic degradation 2. Uptake into 1) neuron via specific membrane transport protein, then uptake into synaptic vesicles, 2) surrounding astrocytes 3. Diffusion away from synaptic cleft