Topic 2- cells and signalling

Question 1

List the different basic structures of animal cells.

Answer 1

Nucleus
Nucleolus
Ribosomes
Rough endoplasmic reticulum
Smooth endoplasmic reticulum
Gogli apparatus
Mitochondria
Lysosomes
Cytoskeleton

Question 2

Define the nucleus.

Answer 2

Membrane-bound structure containing most of the genetic material.

Question 3

Define the nucleolus.

Answer 3

Within the nucleus, composed of proteins and nucleic acid.

Question 4

Define ribosomes.

Answer 4

Ribonucleic acids and proteins in the cytoplasm involved in the manufacture of proteins.

Question 5

Define the rough endoplasmic reticulum.

Answer 5

Membranous network studded with ribosomes involved in protein synthesis.

Question 6

Define the smooth endoplasmic reticulum.

Answer 6

Membranous network involved in lipid synthesis, regulation of calcium and metabolism of carbohydrates.

Question 7

Define the golgi apparatus.

Answer 7

Sorts and chemically modifies proteins for specific uses.

Question 8

Define the mitochondria.

Answer 8

Membrane enclosed organelle responsible for generating chemical energy.

Question 9

Define lysosomes.

Answer 9

Contains enzymes to remove waste.

Question 10

Define the cytoskeleton.

Answer 10

Made up of different tube like structures, responsible for maintaining shape of a cell.

Question 11

Explain the different types of cells within the nervous system.

Answer 11

There are specialised cells in the nervous system which can be divided into glia and neuron cells. The glia can be further divided into macroglagia, microgalgia, epindymal cells and satellite cells. The macrogalgia can be divided into astrocytes and Oligodendrocytes (found in the central nervous system) or Schwann cells (found in the peripheral nervous system).

Question 12

Explain what astrocytes are.

Answer 12

Astrocytes are a type of microglia.These cells have several important functions including:

Regulating local supply of oxygen and glucose to neurons.

Providing structural support and stability to neurons.
Mopping up leaked or excessive chemical messengers (neurotransmitters).

Regulating the concentration of potassium ions (K+).

They also appear to have a fundamental role in brain signalling (research is still being conducted to support this).

Question 13

Explain what oligodendrocytes are.

Answer 13

They are a type of macroglia that act as insulators and are found in the central nervous system. Its counterpart in the peripheral nervous system is the Schwann cell. These cells have several important functions including:

Form rows of semi-rigid tissue between neurons which is believed to provide structural support.

Supply nutrients to neurons.

Provide myelin sheaths (a fatty layer that surround. neurons).

Question 14

Explain what satellite cells are.

Answer 14

Satellite cells are surround sensory neurons in the PNS and perform several functions:

Regulate the extracellular chemical environment.

Protect, nourish and maintain neurons.

Highly sensitive to injury and inflammation, and are associated with neuropathological states, such as chronic pain.

Question 15

Explain what microglia are.

Answer 15

The second major class of glia cells, is microglia. Microglia have a range of functions including:

Acting as brain scavengers engulfing and destroying bacteria and debris from dead and dying neurons and glia.

Remodelling the nervous system during development

Secreting chemicals important in glial cell and blood vessel formation

Responding to immune system activation and neurodegeneration

Question 16

What are ependymal cells?

Answer 16

Ependymal cells form a layer lining the brain ventricles and the central canal of the spinal cord. They are one of the sources of cerebral spinal fluid – they secrete it and may assist in its circulation.

Question 17

Explain neurons.

Answer 17

Each neuron is capable of signalling with tens of thousands of other neurons, which means there are a lot of signals whizzing around our nervous systems.

To make this possible, the neuron has extensive support from glial cells (which outnumber neurons 10:1) and has several specialised structural features.

Question 18

Explain the features of neurons.

Answer 18

The cell body: contains most of the key organelles e.g. nucleus.

Dendrites: protrude from cell body region, point of incoming information to neuron, pass signals to cell body for processing

Axon: Sends signal down to axon terminals, has yellow patches (myelin sheath- insulating).

Nodes of ranvier: gaps between myelin sheath.

Question 19

Explain the neuronal membrane.

Answer 19

Phospholipid bilayer: double layer of lipid molecules with phosphates attached. Semi-fluid; allows some movement.

Some proteins such as peripheral protein sits to one side while others such as the integral or globular protein span the entire membrane

Protein channels: open and close to send signals.

Question 20

What is the charge of the intracellular space of the axon?

Answer 20

Negatively charged overall
Sodium- 10mM
potassium- 140mM
negatively charged proteins

Question 21

What is the charge of the extracellular space of the axon?

Answer 21

positively charged overall
Sodium- 142mM
potassium- 4mM
negatively charged proteins

Question 22

Explain the forces across the membrane at rest.

Answer 22

The difference in charge across the membrane (i.e. the fact that one side is negative and one side is positive), sets up an electrostatic gradient that creates forces acting on the different chemicals

Opposites attract so anything with a positive charge wants to be in a negatively charged space and anything with a negative charge wants to be in a positively charged space.

K+ and Na+ are both positively charged ions and therefore the electrostatic gradient creates a force that would have them move into, or stay in, the cell.

Given that most of the K+ is already inside the electrostatic force would only act to keep it there. But there is a strong force on Na+ for them to move into the cell as most of the sodium is outside the cell.

Question 23

Explain leaky membranes in the resting cell.

Answer 23

Although sodium and potassium ions do not freely pass through the membrane at rest some can move through ‘leaky channels’. These allow the ions to leak across the membrane.

The membrane is naturally more permeable to potassium than sodium so more can leak through the membrane. Even though the two forces acting on potassium are opposing there is still a small amount of movement of potassium out of the cell at rest, which helps keep the cell negative because potassium takes it’s positive charge out of the cell when it leaks out, making the inside more negative.

Sodium leaks through less easily than potassium. But it moves according to the diffusion and electrostatic forces so movement is into the cell, making the cell positive.

The cell must be kept negative and we must have more sodium outside than in so this leaking must be countered.

Question 24

Explain the role of the sodium potassium pump.

Answer 24

To counter the movement of ion through the channels and prevent the concentrations of ions becoming incorrect and to help keep the inside negative, there is an active pump:

The sodium potassium transporter is also called the sodium potassium pump or the sodium potassium ATP pump.

Moving against the concentration gradient is an active process so requires energy, unlike diffusion.

The pump transports 3 sodium ions out of the cell (countering the leakage of sodium in) for every 2 potassium ions it transports into the cell (countering leakage out).

This ensures sodium and potassium stay at the correct concentrations but also results in a net loss of positive charge, keeping the cell negative (around -70mV).

Question 25

Explain voltage gated channels.

Answer 25

These are ion specific and they open and close when the potential difference or charge across the membrane reaches specific levels. At rest they are all closed, leaving only the leaky channels, and the pump, to move ions across the membrane. But with a small activation, they can burst into coordinated opening and closing. This is what happens when the cell fires, spikes or produces an action potential – all terms used for a nerve impulse. Action potential is when there's a rapid change in membrane potential.

Question 26

Explain the depolarisation phase of the action potential.

Answer 26

At rest the membrane is said to be polarised with the inside more negative than the outside. If there is sufficient stimulation, there is depolarisation. This is where the polarisation is reversed, i.e. the inside becomes positive. At around +40 mV the cell moves into a phase of being repolarised i.e. it returns to its original polarised state with the inside being more negative. Finally, there is a period of hyperpolarisation when the cell is even more negative than it was at rest. In about 4 milliseconds, the voltage goes from -70 to +40 and then back down, dipping lower into a more negative charge before going back to -70 again.

Question 27

Explain the repolarisation phase of the action potential.

Answer 27

This phase happens after depolarisation. This is caused by the movement of potassium; sodium has flooded into the cell in the polarisation period and by the time of the action potential peak the potassium cells are fully open, allowing potassium to leave the cell freely. It is the coordinated movement of ions through voltage-gated channels that create these phases: Voltage-gated potassium channels remain open when the sodium channels have shut and potassium now flows freely out of the cell down its concentration gradient but also now pushed out by an electrostatic force created when the influx of sodium turned the inside positive, repelling the positively charged potassium ion as like charges repel. As the membrane approaches its resting potential again, the voltage-gated potassium channels close. At this point the sodium channels re-set and come out of their absolute refractory period, meaning they could open again if the threshold is reached.

Question 28

Explain the hyperpolarisation phase of the action potential.

Answer 28

It is coordinated movement of ions through voltage-gated channels that create these phases: Due to the slow closure of the voltage-gated potassium channels, some extra potassium manages to escape resulting in an even more negative internal environment. This period is referred to as the relative refractory period because, although the sodium channels are now able to open again, they are further from the threshold than they normally are at rest, meaning a much bigger stimulus is required for them to fire again. The timing of the refractory periods means that the maximum firing rate of most neurons is around 1000 times per second or 1 KHz. To return to the resting state, the sodium potassium transporter must work to switch the ions back round to their original concentrations- bring all the sodium outside and all the potassium inside.

Question 29

Explain the repolarisation phase of the action potential.

Answer 29

This phase happens after depolarisation. This is caused by the movement of potassium; sodium has flooded into the cell in the polarisation period and by the time of the action potential peak the potassium cells are fully open, allowing potassium to leave the cell freely. It is the coordinated movement of ions through voltage-gated channels that create these phases: Voltage-gated potassium channels remain open when the sodium channels have shut and potassium now flows freely out of the cell down its concentration gradient but also now pushed out by an electrostatic force created when the influx of sodium turned the inside positive, repelling the positively charged potassium ion as like charges repel. As the membrane approaches its resting potential again, the voltage-gated potassium channels close. At this point the sodium channels re-set and come out of their absolute refractory period, meaning they could open again if the threshold is reached.

Question 30

Explain the importance of the myelination using MS.

Answer 30

The importance of myelination is clear when you consider the impact of multiple sclerosis (MS) on individuals. MS is an autoimmune condition in which the body’s immune system attacks the myelin that surrounds the axons. It's a degenerative brain disease It's most commonly diagnosed in people in their 20s and 30s. It's more common in women than men.

Question 31

Explain the importance of the myelination using MS.

Answer 31

The importance of myelination is clear when you consider the impact of multiple sclerosis (MS) on individuals. MS is an autoimmune condition in which the body’s immune system attacks the myelin that surrounds the axons. It's a degenerative brain disease which causes a creeping paralysis. It's most commonly diagnosed in people in their 20s and 30s. It's more common in women than men.

Question 32

What is the typical threshold value for an action potential to be triggered?

Answer 32

-55mv

Question 33

What is the typical threshold value for an action potential to be triggered?

Answer 33

-55mv

Question 34

What happens when the action potential reaches the end of the axon?

Answer 34

Once the action potential reaches the end of the axon and the terminal regions, it cannot travel any further. There is a physical gap between neurons and the signal must travel across the gap – synaptic gap. To do that it must be converted into a chemical signal. This happens at the chemical synapse. the chemical synapse consists of a pre-synaptic and post-synaptic neuron. The pre-synaptic neuron is the one carrying the original action potential and the post-synaptic one receives the stimulus.

Question 35

Explain the structure of the pre-synaptic and post-synaptic neuron.

Answer 35

In the presynaptic neurons there are vesicles containing neurotransmitters- the key chemical signals of the nervous system. These vesicles go through a constant process of recycling so that the contents can be packaged and stored until needed. The presynaptic neuron also contains voltage-gated calcium channels and a reuptake channel/transporter. On the post-synaptic neuron there are specific receptors which will only work for a particular neurotransmitter like a lock and key.

Question 36

Explain the receptors found in the post-synaptic neuron.

Answer 36

There are 2 different types of receptors that can be found in the post-synaptic neuron; ionotropic and metabotropic. Ionotropic/direct gating receptors: the place where the neurotransmitter binds to the receptor is one structural unit so the moment it binds the channel can open- there is a very quick process between the neurotransmitter bonding to the receptor and the ions starting to move across the membrane. Metabotropic/indirect gating receptors: the neurotransmitter binds to a receptor which triggers other cellular events involving a G protein. Eventually a channel somewhere else is open- this process takes longer as the neurotransmitter binds in one place and starts of a series of smaller reactions which result in an ion channel elsewhere opening. The metabotropic receptors can be useful as the reaction can be amplified- in the ionotropic receptors one neurotransmitter can open one channel however over here the neurotransmitter binding will set off a cascade of events which could result in a large number of ion channels happening, amplifying the signal.

Question 37

Explain how post-synaptic potentials are combined.

Answer 37

When the post-synaptic neuron receives the different potentials, it has to add them all up in some way. It can add things up in two ways- the post-synaptic potentials are integrated across time and space: Temporal summation: repeated inputs from the same place in quick succession will add up (add over time). Spatial summation: inputs arriving in different places simultaneously are added together (add over space). All inputs into the cell have to be combined. If after adding them all up we find the cell has an overall depolarisation, moving it nearer to the threshold for action potential, that is a positive effect on the cell. If it has hyperpolarisation it is less likely the produce an action potential. there are likely to be several failed initiations where the neuron received some excitatory potential but not enough to produce action potential.

Question 38

How are neurotransmitters removed from the synapse?

Answer 38

Despite whether or not an action potential occurs, at some point the neurotransmitter needs to be turned off. This can be done in different ways: Enzymes: can break up the neurotransmitter molecules into ingredients that can be recycled to be used again later by the nervous system Reuptake channel: pre-synaptic neuron can actively take back some of the neurotransmitter it has released and put it into vesicles for use again in the future Diffusion: simplest method- neurotransmitter can diffuse away from the synapse. If it isn't near the receptors then it cannot bind to them Glia mop up: astrocytes can mop up extra neurotransmitter Different neurotransmitters use different methods to be removed from the synapse.

Question 39

What are neurotransmitters?

Answer 39

Neurotransmitters are defined as: A chemical that must be synthesized in the neuron or otherwise be present in it. A chemical that must be released when a neuron is active and produce a response in some targets (typically the post-synaptic receptors) The same response must be obtained when the chemical is experimentally placed on the target. A mechanism must exist for removing the chemical from its site of activation after its work is done.

Question 40

How do we classify neurotransmitters?

Answer 40

There are three types of neurotransmitters: amino acids, monoamines and ‘other’. Amino acids: glutamate and gamma-aminobutyric acid (GABA) Monoamines: dopamine, noradrenaline (norepinephrine) and serotonin Other: acetylcholine

Question 41

Explain the amino acid of glutamate.

Answer 41

Glutamate is found throughout the brain rather than in a few specific pathways. Key information about this neurotransmitter is: It is produced from the amino acid glutamine and this is the rate-limiting step- the availability of glutamine determines how much glutamate we can make. Glutamine is taken into mitochondria and the actions of an enzyme called glutamanase turn it into glutamate. It is then pumped into vesicles using a vesicular transporter and held there until it is needed. Once released into the synapse it can bind to post synaptic receptors but is also taken up by glutamine transporters which are found in neurons, glia cells and astrocytes. Once taken up into the astrocyte, glutamate is broken back down by an enzyme called glutamine synthetase into glutamine which is then put back into the system to make more glutamate elsewhere. When in the synapse, glutamate can bind to several different types of receptors. three of those are ionotropic known as NMDA and AMPA kinate receptors. It can also bind to a metabotropic receptors known as mGlu. Both of these types of receptors will result in depolarisation of the synaptic neuron when glutamate binds to them. Glutamate is always an excitatory neurotransmitter. Glutamate is critical however due to being omnipresent it is linked to the general functioning of the brain rather than any function in particular. It has been identified to play a role in learning and memory. Glutamate has excitotoxicity- it becomes toxic if found in too great quantities. It will literally excite cells to death if not removed properly from the synapse. This is why astrocytes are very important in mopping up glutamase.

Question 42

Explain the amino acid GABA.

Answer 42

GABA is also found throughout the brain rather than in a few specific pathways. It is made from glutamate and so has the same rate-limiting step as glutamine and is also turned into glutamate in the mitochondria through glutamanase. There is then a second enzyme acting, glutamic acid decarboxylase, which turns glutamate to GABA. From there, GABA is packed into the vesicle until used. After released from vesicles into the synapse, it has similar reuptake mechanism to glutamate but also can bind to both ionotropic and metabotropic receptors. There are referred to as type A and type B respectively. Unlike glutamate, instead of resulting in excitation, GABA always results in a hyperpolarisation of the post synaptic neuron, producing an inhibitory post-synaptic potential, taking the post-synaptic neuron further away from the point where it could fire an action potential.

Question 43

Explain some of the pharmaceutical uses of GABA and glutamate.

Answer 43

Both glutamate and GABA are found everywhere and so rarely linked to specific functions however have been used in pharmacology for drug treatment. GABAergic drugs are used for epilepsy and anxiety Some anaesthetics such as propofol act on GABA by increasing its action Drugs like ketamine block glutamate transmission Lithium treats depression and bipolar and works by reducing glutamate and increasing GABA

Question 44

Explain the monoamine dopamine.

Answer 44

Key information about this neurotransmitter is: It is produced from an enzyme known as tyrosine which udergoes a reaction with tyrosine hydroxylase to produce L-DOPA. L-DOPA is then converted by an enzyme called dopa decarboxylase into dopamine which is stored for release in vesicles. Once released into the synapse dopamine can be taken back up into the synapse by reuptake channels into the pre-synaptic neuron but can also be broken down by monoamineoxydase or COMT, both of which are inhibitors. If the dopamine reaches the receptors without being broken down or taken back up into the pre-synaptic neuron, it will reach two different types of receptors both of which are metabotropic and so gated by G proteins. These are called D1 like and D2 like however there are actually five dopamine receptors in total. D1 tends to be excitatory and D2 tends to be inhibitory. Dopamine can be found in specific pathways in the brain and so unlike glutamate and GABA it isn't just everywhere and we need to consider some special pathways.

Question 45

Explain the different pathways of dopamine.

Answer 45

There are four pathways of interest: All the pathways originate from the midbrain in two areas; the ventral tegmental area and the substantia nigra pass compactor. These two regions contain the dopamine cells which are then projected through four different pathways; the mesocortical pathway, the mesolimbic pathway, the nigrostraital pathway and the tubero-infundinbular pathway. The mesocortical pathway goes from the ventral tegmental area to the prefrontal cortex and is involved in attention and working memory The mesolimbic pathway goes from the ventral tegmental area to the nucleus accumbens and involved in goal directed behaviours The nigrostriatal pathway goes from the substantia nigra pars compacta to the dorsal striatum and is involved in voluntary movement The tubero-infundinbular pathway goes from the ventral tegmental area to the pituitary gland. Dopamine is implicated in several conditions including Parkinson’s disease, Schizophrenia, ADHD and addiction. Drugs that act on dopamine are the main treatments for PD, SZ and ADHD.

Question 46

Explain the monoamine noradrenaline.

Answer 46

Key information about this neurotransmitter is: It is produced from dopamine so has the same rate-limiting step. An extra enzyme called dopamine beta-hydrozylase turns the dopamine into noradrenaline. This can be released and broken down into enzymes or taken back up. If it does bind to receptors, it will bind to either alpha or beta receptors which are both metabotropic. They can have excitatory or inhibitory effects. All noradrenergic neurons are located in the hindbrain in a tiny structure called the locus coeruleus from where they send axons throughout the cortex, meaning noradrenaline is involved in a range of functions including sleep and arousal, pain processing, automatic nervous system functioning and attention. It's also implicated in a number of conditions including parkinsons, ADHD and depression.

Question 47

Explain the monoamine serotonin.

Answer 47

Key information about this neurotransmitter is: It is produced from tryptophan and amino acid through several different stages beginning with the actions of enzyme tryptophan hydroxylase and finishing with aromatic amino acid decarboxylase Once the serotonin is produced it can be released into the synapse and undergo the same breakdown and reuptake as seen for dopamine and nordadrenaline. There are many types of seratonin receptors, most of which are metabotropic. They can have an excitatory or inhibitory effect on the post-synaptic cell. Serotonergic neurons are found in a small structure in the hindbrain called the raphe nucleus, from where they send axons throughout the cortex, meaning they're involved in many different functions including things like risk taking, aggression and mood. The neurotransmitter is linked to things like depression, ADHD and schizophrenia.

Question 48

Explain acetylcholine.

Answer 48

Key information about this neurotransmitter is: The rate limiting step is the uptake of choline. Acetylcholine is made from choline combining with acetyl coenzyme A. It is released into the synapse where is combines with either nicotinic (ionotropic) or muscarinic (metabotropic) receptors. The receptors can have either excitatory or inhibitory actions Once the acetylcholine is released it is broken down by the enzyme acetylcholintesterase. Cholinergic neurons are found in several regions in the brain, most notably pons in the hindbrain and in the basal forebrain from where it has extensie connections to various regions including those important to memory. It is important for things like sleep and attention and is also implicated in Alzheimer's disease.

Question 49

Explain acetylcholine.

Answer 49

Key information about this neurotransmitter is: The rate limiting step is the uptake of choline. Acetylcholine is made from choline combining with acetyl coenzyme A. It is released into the synapse where is combines with either nicotinic (ionotropic) or muscarinic (metabotropic) receptors. The receptors can have either excitatory or inhibitory actions Once the acetylcholine is released it is broken down by the enzyme acetylcholintesterase. Cholinergic neurons are found in several regions in the brain, most notably pons in the hindbrain and in the basal forebrain from where it has extensive connections to various regions including those important to memory. It is important for things like sleep and attention and is also implicated in Alzheimer's disease.

Question 50

Which neurotransmitters can monoamine oxidase not break down?

Answer 50

When monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are not broken down, increasing the concentration of all three neurotransmitters in the brain.

Question 51

What is an antagonist?

Answer 51

A substance that blocks the actions of a natural chemical.

Question 52

Which neurotransmitters can monoamine oxidase not break down?

Answer 52

Glutamate and GABA