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Flashcards in 2 - Cells and Signalling Deck (55):
1

Key organelles in an animal cell (9)

Nucleus

Nucleolus

Ribosome

Mitochondria

Golgi Apparatus

Rough Endoplasmic Reticulum

Smooth Endoplasmic Reticulum

Lysosome

Cytoskeleton

2

Function of the Nucleus

Membrane bound structure containing genetic material

3

Function of the Nucleolus

Lies within the nucleus, is composed of proteins and nucleic acids

4

Function of the Ribosome

Involved in the manufacturing of proteins
Lies in the cytoplasm, composed of ribonucleic acids and proteins

5

Function of the Mitochondria

Membrane-bound organelle responsible for generating ATP

6

Function of the Golgi Apparatus

Sorts and chemically modifies proteins for specific uses

7

Function of the Rough Endoplasmic Reticulum

A membranous network studded with ribosomes and is involved in protein synthesis

8

Function of the Smooth Endoplasmic Reticulum

A membranous network without ribosomes and is involved in lipid synthesis, regulation of calcium and metabolism of carbohydrates

9

Function of the Lysosome

Contains enzymes to remove waste

10

Function of the Cytoskeleton

Made up of different types of tube-like structures responsible for maintaining cell structure

11

Important organelles in cells of the nervous system

Rough Endoplasmic Reticulum
- particularly important since many Neurotransmitters are based on proteins

Mitochondria
- in neurons producing Action Potentials, need a lot of energy

12

2 types of cells in the nervous system

Neurons
Glia
(10x more glia than neurons)

13

Typical Neuron

Dendrites on the cell body (soma)
Axon hillock leads to the axon (with axoplasm in it)
Branching to axon terminals -> terminal boutons -> synapses

14

Neuronal Membrane

Lipid bilayer with protein channels (ion channels)
Selectively permeable via these channels

15

Resting membrane potential

First measured in a giant squid
- one electrode inside the cell and one outside
> realised that the inside is more negative than the outside

- Resting Membrane Potential is about -70mV

- Negatively charged proteins within the cell
- High concentration of Sodium (142mM) and a little Potassium (4mM) outside the cell

16

Forces across the membrane

Outside the cell:
- 142mM [Na]+ and 4mM [K]+

Inside the cell:
- 10mM [Na]+ and 140mM [K]+ AND negatively charged proteins

Thus:
- Concentration gradient and Potential gradient for [Na]+ into the cell
- Concentration gradient for [K]+ going out of the cell

17

Maintaining the Resting Membrane Potential (3 mechanisms)

- The membrane is more permeable to Potassium than Sodium so there is a more diffusion of [K]+ out of the cell than [Na]+ into it, so there's a net loss of positive charge
- Sodium-Potassium Pump removes 3 [Na]+ and brings in 2 [K]+, so there's a net loss of positive charge
- Negative proteins in the cell cannot leave, so maintain the negative charge

18

Sodium Channels and the Action Potential

- Initially Sodium channels are closed and the Resting Membrane Potential is -70mV
- A change in the membrane potential of -55mV causes Sodium channels to open, and [Na]+ floods into the cell down it's concentration and potential gradient
- The newly positive potential membrane (+30mV) causes the Sodium channels to close and become Inactivated (ball and chain)

19

Potassium Channels and the Action Potential

- The Potassium channels have voltage sensitive paddles which are positively charged
- So at Resting Membrane Potential (-70mV), the paddles are held shut
- Due to the opening of Sodium Channels and subsequent influx of Sodium, the membrane potential is (+30mV) which causes these paddles to open by repulsion
- Thus potassium ions leave down the concentration gradient, out of the cell, and also down the newly created potential gradient
- making the inside of the cell negative again

20

The Action Potential Process

- Resting Membrane Potential (-70mV)
- change in potential to Threshold Voltage (-55mV) {at 0ms}
- causes Depolarisation (opening of voltage-gated Sodium Channels)
> [Na]+ floods into the cell down concentration and potential gradient, causing the inside of the cell to become positive
- at +30mV membrane potential, the Sodium Channels become inactivated and the voltage-gated potassium channels open, allowing [K]+ to flood out of the cell, down its concentration and potential gradient, causing the inside of the cell to become more negative - Repolarisation
- After the membrane potential reaches resting level {3ms}, the Potassium channels remain open briefly, causing Hyperpolarisation
- This is corrected via the Sodium-Potassium pump, and general diffusion across the cell membrane, to reach Resting Membrane Potential again {4-7ms}

- The action potential propagates along the axon

21

Refractory Periods

- During the absolute refractory period, no subsequent Action Potentials can be formed, this is because until Hyperpolarisation starts, the Voltage-Gated Sodium Channels are Inactivated (ball and chain)
- During the Relative Refractory Period (from Hyperpolarisation to RMP), the Potassium channels are activated so can produce an Action Potential, but since the Membrane Potential is Hyperpolarised, it will take a larger-than-normal trigger to reach the threshold voltage

22

Factors affecting Conduction Velocity (3)

Temperature:
- hotter = faster

Axon Diameter:
- the wider the axon, the less resistance for ion movement, so the action potential propagates faster

Myelination:
- the fatty sheath provides insulation so there is less leakage of current out of the axon

23

Cells of the Nervous System

Glia and Neurons

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Types of Glia

Macroglia
Microglia
Ependymal Cells
Satellite Glial Cells

25

Types of Macroglia

Oligodendrocytes / Schwann Cells
Astrocytes

26

Types of Synapse

Chemical
- most common
- unidirectional
- relatively slow
- diversity of effects

Electrical
- rare
- fast
- can be bi-directional

27

Signalling at a chemical synapse

- Action potential arrives at the axon terminal
- causing Voltage-Gated [Ca]2+ channels to open
- [Ca]2+ enters the cell and causes vesicles (containing NT) to move to the pre-synaptic membrane
- these vesicles fuse to the membrane and release their Neurotransmitter via Exocytosis
- Neurotransmitter diffuses across the Synaptic Cleft and onto receptors on the Post-synaptic membrane

28

Types of Cellular Receptors

Ligand-gated (ionotripic) receptors
- fast
> neurotransmitters bind to receptors on the channel, causing the channel to open

G-Protein linked (metabotropic) receptors
- slow but amplifying
> neurotransmitter binds to a receptor, causing G-Protein activation
> the G-protein activates an Effector Protein which causes the Ion Channel to open

29

Postsynaptic Effects

Can either be Excitatory or Inhibitory, depending on the Neurotransmitter and Receptor
- If the overall impact makes the inside of the cell more positive and it reaches the threshold value (-55mV) this will trigger a Post-Synaptic Action Potential

30

Summation

Spatial Summation
- inhibitory / exhibitory post-synaptic potentials from different locations on the neuron's cell body (mostly on the dendrites) sum to determine whether an Action Potential Will Fire

Temporal Summation
- Post-synaptic Potentials firing one after another also sum

31

Neurotransmitter Removal from the Synaptic Cleft (3)

- Reuptake into the presynaptic neuron
- Enzymic breakdown so NT can no longer activate the Receptor
- Diffusion away from the synapse

32

Acetylcholine (ACh)

- the first neurotransmitter discovered
- Nicotinic (ionotropic) receptor
- Glucose is the precursor
- Excitatory or Inhibitory depending on the receptor

33

Rate Limiting Step in ACh production

The uptake of Choline via the action of Acetylcholine Esterase (on ACh)

34

Cholinergic Pathways and Function

Central Nervous System:
- One set of neurons is in the Pons
> involved in dreaming and sleep processes
- Another set of neurons in the Basal Forebrain
> to do with learning

The 'sets' are comprised of the cell bodies of Cholinergic Neurons, the axons travel all over the brain (pathways)
- including the Hippocampus, for Memory

Peripheral Nervous System:
- Somatic
> ACh is the main neurotransmitter between motor neuron and muscle
- Autonomic
> ACh is a key NT in Sympathetic and Parasympathetic pathways

35

Acetylcholine and health

- some paralytic poisons target ACh receptors / production (since it is heavily involved in the somatic NS)
- involved in smoking (nicotine binds to nicotinic receptors)

Myasthenia Gravis:
- autoimmune
- a weakness in muscles primarily innervated by cholinergic neurons

Alzheimer's:
- degeneration of cholinergic neurons
(as with other neurodegenerative diseases)

36

Glutamate (Glut)

- synthesised from Glutamine
- Rate Limiting Step is the supply of amino acids that Glutamate is made from

- Ionotropic Receptors:
> NMDA
> AMPA
> Kainate
- and Metabotropic Receptors:
> mGluR

- Glutamate neurons are found all over the brain, are always excitatory, and too much Glutamate is toxic, so needs to be quickly removed
> this is done by Glial Cells (particularly Astrocytes), which break Glutamate into Glutamine with Glutamine Synthetase

37

GABA

- synthesised from Glutamate
- rate limiting step is the supply of amino acids that make Glutamate


- Type A receptors (ionotropic)
- Type B receptors (metabotropic)
- Always Inhibitory

GABA neurons and axon terminals are found throughout the brain

38

GABA and Glutamate in health

- GABAergic drugs are used to treat epilepsy (seizures) and anxiety
- Anaesthetics increase GABA action
- drugs like Ketamine block glutamate transmission
- Lithium reduces glutamate and increases GABA
- both mediate the effects of alcohol
- both have some links to suicide

Since GABA and Glutamate pathways are everywhere, drugs that effect them effect the whole body

39

Dopamine (DA)

- synthesised from Tyrosine
- rate limiting step is the action of Tyrosine Hydroxylase
- taken back up by MAO and COMT in the Liver

- D1 like receptors
- D2 like receptors
> both are metabotropic

40

Dopamine pathways and function

Nigrostriatal Pathway
- from the Substantia Nigra Pars Compacta (SNc) to the Dorsal Striatum
- involved in voluntary movement

Mesolimbic & Mesocortical pathways
- both from the Ventral Tegmental Area (VTA) (central, hence meso-)
- Mesolimbic goes to the Ventral Striatum (Nucleus Accumbens {NAc})
- Mesocortical goes to the Prefrontal Cortex
- involved in working memory / attention / motivation / goal-directed behaviour / addiction

41

Noradrenalin (NA)

- synthesised from Tyrosine
- rate limiting step is the synthesis of Tyrosine Hydroxylase
- taken up by MAO and COMT

- alpha-receptors and beta-receptors
- both are metabotropic

42

Noradrenergic Pathways and function

- a small amount of NA production in the brain is done by cell bodies in the Locus Coerulus
- critical for Sympathetic Nervous System
- linked to arousal and sleep
- descending pain control
- linked to attention

43

Serotonin (5HT)

- synthesised from Tryptophan (comes from diet)
- rate limiting step is the action of Tryptophan Hydroxylase
- many different receptors, all are Metabotropic
- removed by MAO and COMT

44

Monoamines

Dopamine and Noradrenaline (and Serotonin)

45

Serotonin Function and Pathway

- cell bodies in the Raphe Nuclei
- pathways all around the brain
- involved in sleep-wake cycle (5HT activation is associated with wakefulness)
- though to reduce risk taking behaviour
- linked to aggression
- descending pain control

46

5HT and health

- psychoactive drugs
- OCD
- depression

47

Process of neurotransmission

- acquisition of precursor
- synthesis of NT via enzymes
- intracellular metabolism of other products
- vesicular storage of NT
- release into synapse
- receptors
> antagonists block action of NTs
> agonists mimic the action of NTs
- reuptake into pre-synaptic membrane
- enzymic breakdown

48

Drug administration

Oral:
- easy, self administered, but must be able to withstand breakdown by digestive enzymes
- low bioavailability due to first pass metabolism in the Liver, thus reduced levels reach the brain

Intravenous:
- has to be done by a professional
- 100% bioavailability, but a risk due to the speed and concentration

Inhalation:
- quick absorption of drug into the blood due to high surface area of the lungs
- risk of damage to nasal passages and lungs
- can be self-administered

49

Speed of drug administrations

- IV
- Intramuscular
- Subcutaneous
- Oral
- Rectal
- Transdermal (very slow)

50

Blood Bran Barrier

- tightly connected endothelial cells that protect the brain from substances
- prevents NTs from passing out, and maintains a constant brain environment
- substances must be very small and lipid-soluble to pass through
> alcohol and barbiturates (CNS depressants) pass through easily

51

Drug development (4 stages)

Stage 1
- small number of healthy volunteers
- determines the range of required dosages and side-effects

Stage 2
- conducted in patients with the condition
- normally double blind RCT
- used to test tolerance, safety and efficacy (ability to produce the intended result)

Stage 3
- large number of patients with the condition
- further test of tolerance, safety and efficacy
- license for human use can be applied for

Stage 4
- after drug licensing, used in large number of patients
- information about side effects, safety and long-term risks and benefits
- ongoing information

52

Macroglia (2)

Astrocytes
- regulate oxygen and glucose supply to neurons
- provide structural support
- ingest excess NT (particularly Glut)
- regulate K+ concentration

Oligodendrocytes / Schwann Cells
- Oligodendrocytes in the CNS
- Schwann Cells in the PNS
- myelin sheaths
- structural support
- supply nutrients

53

Microglia

- Macrophages that engulf and destroy bacteria and debris from dead and dying neurons and glia
- role in remodelling the NS during development
- secrete chemicals involved in the formation of Glial Cells and Blood Vessels
- respond to Immune System Activation
> thus are involved in neurodegeneration

54

Ependymal Cells

- Glial cells that form a layer lining in the brain ventricles and the central canal of the spinal cord
- sources of CSF

55

Satellite Cells

- Glial cells that surround neurons in sensory, parasympathetic and sympathetic neurons of the PNS
- protect and nourish neurons
- regulate the extracellular environment
- highly sensitive to injury and inflammation