3.7.3 Evolution may lead to speciation

Individuals within a population of a species often show a wide range of variation in their phenotypes - this is due to both genetic and environmental factors. Variation often results from a mutation and further variation results from meiosis and the random fertilisation of gametes during sexual reproduction. We need to know about a few ways in which we can get variation; genetic factors, and environmental factors.

Genetic factors:
It is important to recognise that within a population all members have the same genes. Genetic differences occur as members have different alleles of these genes. Genetic variation arises from:

• Mutations: sudden changes to genes and chromosomes. These may be passed on to the next generation.
• Meiosis: Produces new combinations of alleles before they are passed onto gametes
• Random fertilisation of gametes: Produces new combinations alleles. The offspring are therefore different to the parents. Which gamete fuses with which at fertilisation is also random adding to the variety of offspring two parents can produce.

Environmental factors:

A lot of variation is due largely to environmental influences. Environmental influences include 

 climatic conditions, pH, and food availability. These influences affect the way the organisms genes are expressed. E.g a flower might have a gene to be tall but if it grows in low light then it will not be tall, it will be short. It is important to realise that some characteristics blend into one another forming a continuum (for example, mass and height). Characteristics that display this type of variation are not controlled by a single gene but by many (polygenes). Environmental factors play a major role in determining where on the continuum an organism lies. E.g. individuals genetically predetermined to be the same height may grow to be different heights due to variations in environmental factors (such as diet). This type of variation is the product of polygenes and the environment. If we measure the heights of a large population of people and plot the number of individuals against heights on a graph we will probably obtain a bell-shaped curve known as a normal distribution curve. 

Natural selection

The environmental factors that limit the population of a species are called selection pressures. These include predation, disease, and competition. Selection pressures determine the frequency of all alleles within the gene pool (a gene pool is the total number of all the alleles of all the genes of all the individuals within a particular population at a given time). The process of evolution by mean of natural selection depends upon a number of factors:

• Organisms produce more offspring than can be supported by the available supply of food/light/space...etc
• There is genetic variety within the populations of all species
• A variety of phenotypes that selection operates against

Populations rarely increase in size at such a rate, meaning that death rates must be high. High reproductive rates have evolved in many species to ensure a sufficient large population survives to breed and produce the next generation. This compensates for a high death rate from e.g. predation, competition (for food and water), extremes of temperature, natural disasters such as earthquakes/fires, and disease. Some species have evolved lower reproductive rates and a higher degree of parental care - lower death rates that result help to maintain their population size. 

Ultimately, there are too many offspring for the available resources meaning there is intraspecific competition amongst individuals for the limited resources available. The greater the numbers of offspring the greater this competition is and the more die int he struggle to survive. These deaths are not random. It follows that in a population individuals best suited to the prevailing conditions (e.g better able to escape from predators/catch prey/obtain light/resist disease/find a mate) are more likely to survive than those less well adapted. These individuals are more likely to breed and pass off their more favourable allele combinations to the next generation which will therefore have a different allele frequency than the previous generation. The population will have evolved a combination of alleles that are better adapted to the prevailing conditions. This selection process does depend on individuals of a population being genetically different from one another.

Variation provides the potential for a population to evolve and adapt to new circumstances. Conditions change over time. Having a wide range of genetically different individuals in the population means that some will have the combination of genes needed to survive in almost any new set of circumstances. Populations sowing little individual genetic variation are often more vulnerable to new diseases and climate changes. It is also imperative that a species is capable of adapting to changes resulting from the evolution of other species (e.g if their predators become faster, they must be better adapted to hiding). All in all, the larger a population is and the more genetically varied the individuals within it the greater the chance that one/more individuals will have the combination of alleles that lead to a phenotype which is advantageous in the struggle for survival. These individuals are more likely to breed to produce offspring and pass on their more favourable allele combinations. 

So there are three types of selection that we need to know about:

• Directional selection changes the phenotypes of a population by favouring phenotypes that vary in one direction from the mean of the population. Basically, selection for one extreme phenotype.
• Within a population there is a range of genetically different individuals in respect of any one phenotype. This continuous variation forms a normal distribution curve (a bell shaped curve). This curve has a mean that represents the optimum value for the phenotypic characteristic under the existing conditions.
• If the environmental conditions change the optimum value for survival will change. Some individuals (either left or right of the mean) will pass on a combination of alleles with the new optimum for the phenotypic character. This results in the mean moving to either the left or right of its original position.
• Directional selection results in one extreme of a range of variation being selected against in favour of the other extreme/the average.
• Stabilising selection preserves the average phenotype of a population by favouring average individuals. Basically, selection against the extreme phenotypes.
• Stabilising selection tends to eliminate the extremes of the phenotype range within a population and with it the capacity for evolutionary change.
• Tends to occur where the environmental conditions are constant over a long period of time
• An example is fur length in mammalian species. Individuals with shorter fur will be advantageous hotter years because they can lose body hear more rapidly whilst individuals with longer fur will be advantageous in colder years. If the temperature is a constant 10 degrees neither extreme will be at an advantage and they will be select against those with average fur length.
• The mean is constant but there will be fewer individuals at each extreme
• Disruptive selection favours individuals with extreme phenotypes rather than hose with phenotypes around the mean of the population.
• This is the opposite of stabilising selection
• It favours extreme phenotypes at the expense of the intermediate phenotypes
• This is the most important in bringing about evolutionary change (although it is the least common form of selection).
• It might arise if temperatures alternate between extreme highs and lows in summer and winter, respectively. This might ultimately lead to two separate species of the mammal (one with long fur which is active in winter, and one with short fur which is active in summer).

Allelic frequency

We know that the gene pool is all the alleles of all the genes of all the individuals in a population at a given time. The number of times an allele occurs within a gene pool is referred to as the allelic frequency. The allelic frequency is affected by selection and selection is due to environmental factors. This in turn means that environmental changes therefore affect the probability of an allele being passed on in a population and hence the number of times it occurs within the gene pool. 

NOTE: environmental factors fo not affect the probability of a particular mutant allele arising. All they do is affect the frequency of a mutant allele that is already present in the gene pool.

Speciation

Speciation si the evolution of new species from existing ones. A species is a group of individuals that have a common ancestry and so share the same genes but different alleles and are capable of breeding to produce fertile offspring. Basically, members of a specie are reproductively separated from other species. The most important way i which new species are formed is through reproductive separation followed by genetic change due to natural selection. 

Suppose that a population becomes separated and undergoes different mutations. This will result in it becoming genetically different from the other populations. Each population of the original species will experience different selection pressures as the environment will be slightly different. Natural selection will then lead to changes in the allelic frequencies of each population. The different phenotypes each combination of alleles produces will be subject to selection pressures that will lead to each population becoming adapted to its local environment. This is called adaptive radiation and results in changes to the allele frequencies of each population. As a result of these changes to allele frequencies it is possible that  the populations would no longer be able to breed to produce fertile offspring and each population would not be a different species with its own gene pool.

Genetic drift can take place in smaller populations because the genetic diversity is less. The relatively few members possess a smaller variety of alleles than the members of a large population. As these few individuals breed the genetic diversity of the population is restricted to those few alleles in the original population. As there are only a small number of different alleles in the original population there is not an equal chance of each being passed on. Those passed on will quickly affect the whole population as their frequency is high. Any mutation to one of these alleles that is selectively favoured will also more quickly affect the whole population as its frequency will also be high. The effects of genetic drift will be greater and the population will change relatively rapidly making it more likely to develop into a separate species. In larger populations the effect of a mutant allele will be less because its frequency is less in the larger gene pool. The effects of genetic drift will be less and development into a new species is likely to be slower. 

There are two forms of speciation:

• Allopatric speciation
• Describes the form of speciation where two populations become geographically separated. This may be the result of a physical barrier between two populations which prevents them interbreeding.
• Barriers include oceans/rivers/mountain ranges/deserts
• If environmental conditions either side of the barrier vary, natural selection will influence the two populations differently and each will evolve leading to adaptations to their local conditions.
• These changes may take hundreds/thousands of generations but ultimately may lead to reproductive separation and therefore the formation of a separate species
• Sympatric speciation
• This describes the form of speciation that results within a population in the same area, leading them to become reproductively separated

Lastly, there are a few key terms we need to commit to memory regarding isolating mechanisms:

• Geographical - populations are isolated by physical barriers such as oceans/mountain ranges/rivers
• Ecological - populations inhabit different habitats within the same area and so individuals rarely meet
• Temporal - the breeding seasons of each population do not coincide so they do not interbreed
• Behavioural - mating is often preceded by courtship which is stimulated by the colour/markings of the opposite sex/the call/particular actions of a mate. Any mutation which causes variations in these patterns may prevent mating
• Mechanical - Anatomical differences may prevent mating occurring (e.g it may be physically impossible for the penis to enter the vagina)
• Gametic - the gametes may be prevented from meeting due to genetic/biochemical incompatibility
• Hybrid sterility - Hybrids formed from the fusion of gametes from different species are often sterile because they cannot produce viable gametes.

3.7.2 Populations

As we know from 3.7.4, a population is a group of organisms of the same species in a particular area at a particular time that can potentially interbreed. All the alleles of all the genes of all the individuals in a population at a given time are known as the gene pool. The number of times an allele occurs within the gene pool is referred to as the allelic frequency.

The Hardy–Weinberg principle provides a mathematical model, which predicts that allele frequencies will not change from generation to generation. The principle makes an assumption that the proportion of dominant and recessive alleles of any gene in a population is constant from one generation to the next. This can be the case if the following conditions are met:

No mutations arise

The population is isolated (there is no flow of alleles into or out of the population)

There is no selection pressure (all alleles are equally likely to be passed onto the next generation)

The population is large

Mating with the population is random

A good way of understanding the principle is to look at a gene that has two alleles, a dominant one (A) and a recessive one (b)

Let the probability of allele A = p

Let the probability of the allele a = q

We can write two equations from this. The first is: 

p + q = 1.0

This is because the probability of one plus the other must be 100% (1.0)

There are only four arrangements of the two alleles, AA + Aa + aA + aa. The probability of all four added together must equal 100% (1.0). It follows that…

p² + 2pq + q² = 1

where p is the frequency of the dominant allele and q is the frequency of the  recessive allele of the gene.

3.8.2.1 Most of a cell’s DNA is not translated

In multicellular organisms cells are specialized to perform specific functions. For example red blood cells carry oxygen whilst phagocytes carry out phagocytosis. The process by which cells develop into a specialized structure suited to their function is cell differentiation. In early development all cells are the same. As the organism matures it adapts to the function it will perform when it's mature.

All multicellular cells are derived by mitotic divisions f the zygote (fertilised egg) meaning they all contain the same genes. However, only certain genes are expressed in any certain cell at a time. Certain genes are always expressed such as genes that code for enzymes required for respiration.

As mentioned above, all cells develop from a single fertilised egg. Cells which can differentiate into any body cell (such as fertilised eggs) are known as totipotent cells. In mature mammals very few cells retain the ability to differentiate into any cell - these are known as stem cells. These are undifferentiated dividing cells that must be constantly replaced - they have the ability to divide and form an identical copy of themselves (self-renewal). There are a variety of sources of stem cells in mammals:

• Embryonic stem cells
• Come from embryos in the early stages of development. Can differentiate into any type of cell
• Umbilical cord blood stem cells
• Are derived from umbilical cord blood and are similar to adult stem cells
• Placental stem cells
• Found in the placenta and develop into specific types of cells
• Adult stem cells
• Found in the body tissues of the fetus through to the adult. Are specific to a particular tissue/organ within which they produce the cells to maintain and repair tissues throughout an organism's life

There are a few different types of stem cell we need to know about:

• Totipotent stem cells
• Found in the early embryo
• Can differentiate into any type of cell
• Pluripotent stem cells
• Found in embryos
• Can differentiate into almost any type of cell
• Examples include embryonic stem cells and fetal stem cells
• Multipotent stem cells
• Found in adults
• Can differentiate into a limited number of specialized cells - usually of a particular type (e.g stem cells in bone marrow can poduce any type of blood cell)
• Examples include adult stem cells and umbilical cord lood stem cells
• Unipotent stem cells
• Can only differentiate into a single type of cell
• Are derived from multipotent stem cells and are made in adult tissue
• Examples include cardiomyocytes (muscle cells that make up the cardiac muscle)

Induced pluripotent stem cells (iPS cells)

These are a type of pluripotent cell that is produced from unipotent stem cells. The unipotent stem cell may be almost any body cell. It is then genetically altered to make it acquire the characteristics of embryonic stem cells. To make it aquire the charateristics we induce genes andtranscriptional factors. 

iPS cells are usually not exact copies of embryonic tem cells. They are capacble of self-renewal meaning that potentially they can divide to produce an unlimited supply.

Pluripotent cells in treating human disorders

Pluripotent cells have endless uses. they can be used to treat...

• Burns and wounds (skin cells)
• Heart damage (cardiac muscle cells)
• Muscular dystrophy (skeletal muscle cells)
• Type 1 diabetes (beta cells of the pancreas)
• Parkinsons disease/multiple sclerosis/strokes/Alzheimer's disease/paralysis due to spinal injury (nerve cells)
• Leukaemia/inherited blood diseases (blood cells)
• Osteoperosis (bone cells)
• Osteoarthritis (cartilage cells)
• Macular degeneration (Retina cells of the eye)

3.8.1 Alteration of the sequence of bases in DNA can alter the structure of proteins

When DNA replicates there is a chance of gene mutation. There are 6 types of mutation we need to know...

• Addition
• Insertion of an extra base. This results in a frame shift meaning that most triplets and therefore amino acids will be different - unless 3 bases are added.
• Deletion
• This is the loss of a nucleotide. This causes a frame shift meaning most triplets and therefore amino acids will be different. The polypeptides will therefore be different and a non-functioning protein will most likely result. A deletion at the end of a sequence is likely to have less impact.
• Substitution
• A nucleotide is replaced with (substituted by) another nucleotide. This could...
• Form a stop codon (very bad as polypeptide production would stop for the polypeptide being produced creating an incomplete protein)
• Form a different amino acid (the protein may differ in shape and therefore not function properly. This leads to conditions such as sickle cell anaemia
• The formation of a different codon which produces the same amino acid due to the degenerate genetic code.
• Inversion
• A group of bases separates from the DNA and rejoins in the same position but back-to-front
• Duplication
• One or more bases are duplicated. This has a similar affect to addition mutation therefore produces a frame shift
• Translocation of bases
• A group of bases separates from the DNA sequence on one chromosome and becomes inserted to a DNA sequence on a different chromosome. This often leads to an abnormal phenotype such as reduced fertility and development of certain cancers.

Causes of mutations

Mutations can arise spontaneously during DNA replication. This random and spontaneous occurrence can increase by outside factors known as mutagenic agents (mutagens) including:

• Chemicals
• For example nitrous oxide can directly alter the structure of DNA/interfere with transcription and bemnzopyrene (in tobacco smoke) can inactivate a tumour suppressor gene (TP53) leading to cancer.
• High energy ionizing radiation
• For example, alpha and beta particles and short length radiation such as X-rays and UV light. These can disrupt the structure of DNA.

3.1.4.1 General properties of proteins

Proteins are sort of polymers. They are made of polypeptide chains which are formed from amino acid monomer units. We need to know the structure of an amino acid:

NH2 represents the amine/amino group

COOH represents the carboxyl group

R represents the side chain/group - this is what differs in each amino acid (it is the variable part).

A functional protein often contains 3-4 polypeptide chains. 

Proteins are formed from 3, often 4, structures. These are known as the primary, secondary, tertiary and quaternary structure.

1. Amino acid sequence (polypeptide chain)
2. This sequence is folded into a pleated sheet/alpha helix which is held together by the -NH and -C=O from amino acids (these really form hydrogen bonds twisting the chain)
3. The pleated sheet/alpha helix is further folded into a specific tertiary structure which is bonded by disulphide bridges/ionic bonds/hydrogen bonds
4. Potentially a number of individual polypeptide chains are linked in various ways. They may also be associated with prosthetic (non-protein) groups.

We can test for proteins using the biuret test:

Place a sample of the solution to be tested in a test tube

Add an equal volume of sodium hydrogen solution at room temperature

Add a few drops of dilute copper (2) sulphate solution

Mix gently

Purple = protein

Blue = no protein

3.1.3 Lipids

Two lipids we need to know about are triglycerides and phospholipids. They are organic as they contain carbon (they also contain hydrogen and oxygen). Lipids are insoluble in water but soluble in organic substances (e.g acetone/alcohols). The proportion of oxygen to carbon and hydrogen is smaller than in carbohydrates.

Triglycerides are composed of three fatty acids and a glycerol. They are formed from the condensation of these molecules (three fatty acids and a glycerol) forming an ester bond between the glycerol and each triglyceride. If the R-group of the fatty acid (RCOOH) is said to be unsaturated it just means it has carbon-carbon double bonds (monounsaturated means one carbon-carbon double bond). Fatty acids are hydrophobic.

Phospholipids are composed of two fatty acids, a glycerol, and a phosphate group. The phosphate ‘head’ is hydrophilic and the fatty acid ‘tail’ is hydrophobic. In this way, phospholipids are polar.

Triglyceride structure and function:

High ratio of energy-storing carbon-hydrogen bonds to carbon atoms so are an excellent store of energy

Low mass-energy ratio (much energy can be stored in a small volume)

Large and non-polar = insoluble so does not affect the water potential of cells

Release water when oxidised = provide an important source of water

Phospholipid structure and function:

Polar so form a bilayer in aqueous solutions/environments

hydrophilic heads hold at the surface of the cell-surface membrane

They form glycolipids by combining with the cell-surface membrane which are important in cell recognition

The emulsion test:

Take a dry/grease-free test tube

Add 2cm^3 of the sample and 5cm^3 of ethanol

Shake thoroughly - this dissolves any liquid present

Add 5cm^3 of water and shake gently

Cloudy-white emulsion/colour indicates a lipid is present (clear = no lipid). As a control, repeat with water as the sample.

3.1.2 Carbohydrates

As mentioned in 3.1.1, monosaccharides come together in a condensation to form either a disaccharide/polysaccharide - the bond that forms is a glycosidic bond. There are three disaccharides we need to be aware of:

Maltose is formed from the condensation of two glucose molecules

Sucrose is formed from the condensation of a glucose molecule and a fructose molecule (think like, sucrose is a lot in fruit so FRUctose for FRUit)

Lactose is formed from the condensation of a glucose molecule and a galactose molecule (think gaLACTOSE makes LACTOSE).

There are two isomers of glucose we need to be able to draw,  α-glucose and β-glucose. Here’s what they look like (pretty similar):

There are also three types of polysaccharide we need to know (these are formed by the condensation of many glucose units). Glycogen and starch are formed by the condensation of many α-glucose molecules, whilst cellulose is formed from the condensation of many β-glucose molecules. The structure and function of each polysaccharide is as follows…

Starch

Does not affect the water potential of cells (is insoluble)

Very compact

Branched

1-4 and 1-6 glycosidic bonds

α-glucose

does not diffuse out of cells (large and insoluble)

Glycogen

Does not affect water potential (insoluble)

does not diffuse out of cells (insoluble)

1-4 and 1-6 glucosidic bonds

α-glucose

branched (more than starch)

Cellulose

1-4 glycosidic bonds

inverted β-glucose molecules

straight unbranched chains that run parallel

chains cross-linked by hydrogen bonds forming microfibrils and fibrils add collective strength

Testing for reducing sugars:

Add 2cm^3 of the sample to a test tube (crush in water if not liquid)

Add an equal volume of benedicts reagent

Heat the mixture gently in a water bath for 5 minutes (gently boiling)

clear/blue = trace/none

green = very low

yellow = low

orange = medium

red = high

Testing for non-reducing sugars:

Following a negative benedicts test…

Add 2cm^3 of the sample to a test tube (crush in water if not already liquid)

Add 2cm^3 dilute HCl

place the test tube in a gently boiling water bath for 5 minutes

Slowly add sodium hydrogen carbonate

Test with pH paper to ensure the solution is alkaline

re-test with benedicts reagent.

If reducing sugars are present it is because they were produced from the hydrolysis of non-reducing sugars.

3.1.1 Monomers and polymers

Carbon atoms readily form bonds with other carbon atoms forming a backbone to which other atoms can attach. This means that a large number of different types/sizes of molecules can form (based on carbon). Carbon containing molecules are known as organic molecules.

Chains of individual molecules are known as polymers - the individual molecule being known as a monomer. Examples include saccharides (monosaccharides are the individual unit, polysaccharides are the chain of monomers), amino acids (the amino acid is the monomer, a polypeptide is the polymer), and nucleotides (nucleotides are the monomers, polynucleotides are the polymer). If two monomers are bonded together it is known as a ‘di-‘ (e.g a disaccharide, and a dipeptide)

To join monomers together we use condensation reactions. These bind molecules with the elimination of water when the chemical bond forms.

To break apart polymers into their constituent monomers we add water (known as a hydrolysis reaction) to break the chemical bond formed upon condensation.

3.1.6 ATP

ATP is the main energy source used to carry out processes within cells. It is a phosphorylated macromolecule with three parts:

• adenine (a nitrogen-containing organic base)
• ribose (a sugar molecule with a 5-carbon ring structure (pentose sugar) that acts as the backbone to which other parts are attached
• phosphates - a chain of three phosphate groups

The bonds between these phosphate groups are unstable so they have a low activation energy (this basically means they are easily broken down). When they break they release a considerable amount of energy - often only the last Pi (inorganic phosphate) is broken off. They are broken down by hydrolysis - the addition of water and the reaction is catalyzed by ATP hydrolase:

ATP + water --> ADP + Pi + energy

This is a reversible reaction meaning that energy can be used to add a Pi to ADP to reform ATP (this is the reverse to the reaction above). This reaction is catalyzed by ATP synthase. This is a condensation reaction and can occur in three ways:

• in chlorophyll-containing plants during photosynthesis (photophosphorylation)
• in plant and animal cells during respiration (oxidative phosphorylation)
• in plant and animal cells when phosphate groups are transferred from donor molecules to ADP (substrate-level phosphorylation)

ATP roles:

Okay so this isn't in the spec but we did a lot about it in class so, let me know if you think it is useful for me to write about the roles of ATP/why it is good?

3.1.7 Water

Water is a major component of cells and has several properties that are important in biology. In particular water:

• is a metabolite in many metabolic reactions
• has a relatively high specific heat capacity  meaning it buffers temperature changes. Because the water molecules stick together it takes a lot of inputted energy to break them turning liquid water into a gas. This means it takes a lot of energy to heat a given mass of water meaning water can act as a buffer and resist temperature changes which is good for aquatic animals.
• has a relatively large latent heat of vapourisation. This means that a lot of energy is required to evaporate one kilogram of water. This means that evaporation is effective in cooling because a lot of the body's thermal energy goes into heating a small mass of perspiration (sweat) and the body doesn't lose much water.
• has strong cohesion between water molecules - it is a dipolar molecule made up of two atoms of hydrogen and one of oxygen. The O2 atom has a slightly negative charge whilst the H atoms have a slightly positive charge meaning a water molecule has both negative and positive poles. The negative pole of one water molecule is attracted to the positive pole of another forming a hydrogen bond. this causes water to stick together and have a cohesive nature. This supports columns of water in the tube-like transport cells of plants and produces surface tension where water meets air which provides habitats for organisms such as pond skaters.

Not on the spec but also useful to know, water:

• is a solvent, readily dissolving substances such as gases (O2 and CO2), wastes (ammonia and urea), inorganic ions and small hydrophilic molecules (amino acids, monosaccharides, ATP), and enzymes (whose reactions take place in solution)
• is not easily compressed so provides support e.g turgor pressure and the hydrostatic skeleton of animals
• is transparent meaning aquatic plants can photosynthesise and light rays can penetrate our lenses and the jelly-like fluid that fills eyes so light can reach the retina

3.1.8 Inorganic ions

Inorganic ions occur in body fluids, in solution in the cytoplasm of cells, and also as part of larger molecules (some in high concentrations and some in very low concentrations).

Every inorganic ion has a specific role which depends on its properties. There are a few that we study in detail that we need to be aware of:

• hydrogen ions in pH (here)
• iron ions as a component of haemoglobin (they play a role in transporting oxygen, here)
• sodium ions play a role in the co-transport of glucose and amino acids (here)
• phosphate ions are components of both DNA and ATP (here)

3.6.2.2 Synaptic transmission

The point where one neurone ends and communicates with another/an effector is known as a synapse. Synapses transmit information from one neurone to another by means of chemicals (known as neurotransmitters). In between each neurone is a little gap known as the synaptic cleft in which the first neurone (the presynaptic neurone) releases the neurotransmitter into. Here, the axon is slightly swollen and termed the synaptic knob (this is at the end of the presynaptic neurone). The presynaptic knob contains synaptic vesicles (which the neurotransmitter is stored in), many mitochondria and endoplasmic reticulum (as these are required to  manufacture the neurotransmitter in the axon). The neurotransmitter is released from the synaptic knob into the synaptic cleft where it diffuses across the cleft to the post synaptic neurone which receives it with the help of specific receptor proteins on its membrane - synapses that produce new action potentials in this way are known as excitatory synapses. Synapses can only pass information in one direction only (they are unidirectional) - from the presynaptic neurone to the postsynaptic neurone. 

Summation:
Low frequency action potentials may lead to insufficient concentrations of a neurotransmitter which will not trigger a new action potential in the postsynaptic neurone. This can be overcome by the rapid build up of neurotransmitter in the synapse by summation in one of two methods:

• Spatial summation involves a number of different presynaptic neurones releasing enough neurotransmitter to exceed the threshold value to trigger a new action potential in one postsynaptic neurone
• Temporal summation involves a single presynaptic neurone releasing a neurotransmitter many times over a short period. A new action potential is triggered if the overall concentration of neurotransmitter exceeds the threshold value of the postsynaptic neurone.

Inhibition: 

It is also possible for synapses to make it less likely that a new action potential will be created on the postsynaptic neurone (these are inhibitory synapses):

• The presynaptic neurone releases a type of neurotransmitter that binds to chloride ion protein channels on the postsynaptic neurone
• The neurotransmitter causes the chloride ion protein channels to open and chloride ions move into the postsynaptic neurone (by facilitated diffusion)
• The binding of the neurotransmitter causes potassium protein channels to open and potassium moves out of the post synaptic neurone into the synapse
• the effect of the negatively charged chloride ions moving in and the potassium ions moving out make the inside of the postsynaptic membrane more negative (and the outside more positive)
• The membrane potential increases
• this causes hyperpolarisation making it less likely that a new action potential will be created as a larger influx of sodium ions is needed to produce an action potential

Cholinergic synapse vs neuromuscular junction 

So we need to be able to compare the transmission across a cholinergic synapse and a neuromuscular junction...

Cholinergic synapses

A cholinergic synapse is a synapse in which acetylcholine is the neurotransmitter:

• An action potential arrives at the end of the presynaptic neurone. This causes calcium ion protein channels to open and calcium ions to enter the synaptic knob (facilitated diffusion)
• This influx of calcium ions into the presynaptic neurone causes synaptic vesicles to fuse with the presynaptic membrane and release acetylcholine into the synaptic cleft
• Acetylcholine molecules diffuse across the narrow synaptic cleft and bind to receptor sites on sodium ion protein channels in the postsynaptic neurone membrane
• This causes sodium ion protein channels to open and sodium ions diffuse in rapidly (facilitated diffusion)
• This influx of sodium ions generates a new action potential in the postsynaptic neurone
• Acetylcholinesterase hydrolyses acetylcholine into choline and acetyl (ethanoic acid) which diffuse back across the synaptic cleft into the presynaptic neurone. This also prevents the continuous generation of an action potential in the post synaptic neurone
• ATP released from mitochondria is used to recombine choline and acetyl (ethanoic acid). The acetylcholine is stored in synaptic vesicles for future use
• Sodium ion protein channels close

Cholinergic synapse structure/function:

• has neurotransmitters that are transported by diffusion
• has receptors that cause an influx of sodium ions upon binding with the neurotransmitter
• uses a sodium-potassium pump to repolarize the axon
• uses enzymes to break down the neurotransmitter
• can be excitatory or inhibitory
• links neurone-neurone or neurone-effector organ
• Motor neurones, sensory neurones, and intermediate neurones may be involved
• a new action potential may be produced along the post synaptic neurone
• acetylcholine binds to receptors on the membrane of the postsynaptic neurone

Neuromuscular junctions

This is the point where a motor neurone meets a skeletal muscle fibre. There are many junctions along the muscle to allow the whole muscle to contract at the same time. All muscle fibres supplied by a single motor neurone act together as a unit known as a motor neurone. This means we can control how much force the muscle exerts - e.g if we only want a light force we only stimulate a few units:

• A never impulse is received at the neuromuscular junction and the synaptic vesicles fuse with the synaptic membrane
• Acetylcholine is released into the synaptic cleft and diffuses across to the post synaptic membrane (this is the membrane of the muscle)
• This alters the membranes permeability to sodium ions and sodium ions enter rapidly which depolarizes the membrane
• Acetylcholinesterase hydrolyses acetylcholine into choline and acetyl (ethanoic acid) which diffuse back across the synaptic cleft into the presynaptic neurone. This ensures that the muscle is not over stimulated.

Neuromuscular junction synapse structure/function:

• has neurotransmitters that are transported by diffusion
• has receptors that cause an influx of sodium ions upon binding with the neurotransmitter
• uses a sodium-potassium pump to repolarize the axon
• uses enzymes to break down the neurotransmitter
• only excitatory
• only links neurone-muscle
• only motor neurones are involved
• the action potential ends here
• acetylcholine binds to receptors on the membrane of the muscle fibre

3.6.1.3 Control of heart rate

Nervous organisation
Okay so I can't actually find this in the spec so feel free to skip it out, but there's a little bit about it in my textbook which I've found pretty useful to know for answering exam Qs etc. It basically lets us know about how the nervous system is split up...

So overall we have the nervous system. This has two major divisions:

• the central nervous system (CNS) made up of the brain and spinal cord
• the peripheral nervous system (PNS) made up of pairs of nerved that originate from either the brain or spinal cord. this can be divided into two further subdivisions:
• sensory neurones which carry electrical signals in the form of nerve impulses from receptors towards the central nervous system
• motor neurones which carry nerve impulses away from the CNS to effectors. The motor nervous system can again be divided into two more divisions:
• The voluntary nervous system carries nerve impulses to body muscles and is under conscious/voluntary control
• The autonomic nervous system controls our subconscious/involuntary activities and carries nerve impulses to internal muscles (cardiac and smooth muscle) and glands. You know what's coming... it can be broken down into two more nervous systems which work antagonistically:
• the sympathetic nervous system stimulates effectors therefore speeds up any activity. It helps us to cope with stressful situations thanku sympathetic nervous system) by heightening our awareness and preparing us for activity - many also studying psychology will know this as the flight or fight response.
• the parasympathetic nervous system inhibits effectors and therefore slows down any activity. It controls activity under normal resting conditions (when you're not stressed or anything) and is concerned with conserving energy and replenishing the body's reserves.

Control of the heart rate

Okay so I wanted to get all that said above because basically the activities of internal glands/muscles are regulated by the balance of the sympathetic and parasympathetic nervous systems and control of the heart rate is a good example of this.

Cardiac muscle is myogenic (contraction is initiated within the muscle as apposed to by the nervous system (neurogenic)). In the wall of the right atrium sits a group of cells that are collectively known as the SAN (sinoatrial node) - here the initial stimulus for contraction originates. This has a basic rhythm of stimulation that determines the heart beat rate. The sequence of events that leads to a heartbeat is as follows...

• A wave of electrical excitation spreads out from the SAN across both atria causing them to contract
• A layer of non-conductive tissue prevents the wave crossing to the ventricles. This is known as the atrioventricular septum
• The wave of excitation enters the AVN (atrioventricular node) - a second group of cells which lie between the atria
• After a short delay, this conveys a wave of electrical excitation between the ventricles along a series of specialised muscle fibres (Purkyne tissue) which make up the bundle of His
• The bundle of His conducts the wave through the atrioventricular septum to the base of the ventricles where the bundle branches into smaller fibres of the Purkyne tissue
• The wave of excitation is released from the Purkyne tissue causing the ventricles to contract quickly at the same time from the bottom of the heart upwards

We must of course be able to alter this heart rate e.g if we are running away from our parents. Changes to he heartrate are controlled by the medulla oblongata (a part of the brain). It has two centres. Which centre is stimulated depends on the nerve impulse they receive from two types of receptor which can respond to chemical or pressure changes within the blood:

• one increases heart rate linked to the sinoatrial note by the sympathetic nervous system
• one decreases heart rate linked to the sinoatrial node by the parasympathetic nervous system

Chemoreceptors are found in the wall of carotid arteries. They are sensitive to blood pH changes that result from CO2 concentration changes (more CO2 lowers the pH of blood as CO2 is acidic in solution):

• When the blood has a higher than usual CO2 concentration ifs pH lowers
• chemoreceptors in the walls of carotid arteries detect this and increase the frequency of nerve impulses to the centre in the medulla oblongata
• this centre increases the frequency of impulses via the sympathetic nervous system to the sinoatrial node
• this increases the rate of production f electrical waves by the SAN which increases the heart rate
• the increased blood flow causes more CO2 to be removed by the lungs so CO2 concentration returns to normal
• pH of the blood rises to normal and the chemoreceptors reduce the frequency of the nerve impulses to the medulla oblongata and the medulla oblongata reduces the frequency of impulses to the sinoatrial node which therefore leads to a reduction in heart rate

Pressure receptors occur in the walls of carotid arteries and the aorta:

• when blood pressure is lower than normal pressure receptors transmit more nervous impulses to the medulla oblongata. The medulla oblongata increases the frequency of impulses via the sympathetic nervous system to the SAN which increases the rate at which the heart beats
• when blood pressure is higher than normal pressure receptors transmit more nervous impulses to the medulla oblongata. The medulla oblongata increases the frequency of impulses via the parasympathetic nervous system to the SAN which decreases the rate at which the heart beats

You can calculate cardiac output using the following equation...

cardiac output = heart rate x stroke volume