Cellular physiology

Question 1

Define resting membrane potential

Answer 1

the voltage (charge) difference between the intracellular and extracellular fluid, when the cell is at rest (i.e not depolarised by an action potential).

Question 2

What are the 3 main factors contributing to resting membrane potential

Answer 2

• Chemical gradients generated by active transport pumps: the concentration of ions are significantly different between the intracellular and extracellular fluid, eg. the ratio of potassium ions is 35:1.
• Selective membrane permeability: the cell membrane is selectively ion-permeable, specifically it is much more permeable to potassium ions
• Electrical gradients are generated because potassium leak (via K2P channels) from the intracellular fluid creates a negative intracellular charge. This charge attracts potassium ions back into the cell and thus opposes the chemical gradient.

Question 3

Why is there an electrical gradient between the cell and outside?

Answer 3

• Electrical gradients are generated because potassium leak (via K2P channels) from the intracellular fluid creates a negative intracellular charge. This charge attracts potassium ions back into the cell and thus opposes the chemical gradient.

Question 4

What equation defines the electrochemical equilibrium

Answer 4

Nernst potential

Question 5

Nernst potential means what

Answer 5

• Electrochemical equilibrium develops when electrical and chemical forces are in balance for each specific ion species, and this is described by the Nernst equation.
• The Nernst potential for each ion is the transmembrane potential difference generated when that ion is at electrochemical equilibrium

Question 6

Nernst potential describe the individual potentials of each ion, what descirbe the whole thing?

Answer 6

• The total membrane resting potential for all important ion species is described by the Goldman-Hodgkin-Katz equation, which takes into account the different membrane permeabilities for each ion.

Question 7

Goldman - Hodgkin - Katz are responsive for what?

Answer 7

• The total membrane resting potential for all important ion species is described by the Goldman-Hodgkin-Katz equation, which takes into account the different membrane permeabilities for each ion.

Question 8

What is the resting membrane potential?

Answer 8

• At rest, with normal intracellular and extracellular electrolyte concentrations, the net charge of the intracellular side of the cell membrane is negative, and is approximately -70 to -90 mV for mammalian neurons.

Question 9

What is the Gibbs Donnan effect?

Answer 9

• The Gibbs-Donnan effect describes the unequal distribution of permeant charged ions on either side of a semipermeable membrane which occurs in the presence of impermeant charged ions

Question 10

Why does the Gibbs Donnan effect occur

Answer 10

• The Gibbs-Donnan effect describes the unequal distribution of permeant charged ions on either side of a semipermeable membrane which occurs in the presence of impermeant charged ions

Question 11

At Gibbs Donnan equilibrium what occurs
- On each side of the solution is there electricval neutrality?
- How do you compare realtive amounts of ions?
- Is there a gradient? How would you characterise it?

Answer 11

◦ On each side of the membrane, each solution will be electrically neutral
◦ The product of diffusible ions on one side of the membrane will be equal to the product of diffusible ions on the other side of the membrane
◦ The electrochemical gradients produced by unequal distribution of charged ions produces a transmembrane potential difference which can be calculated using the Nernst equation
◦ The presence of impermeant ions on one side of the membrane creates an osmotic diffusion gradident attracting water into that compartment

Question 12

What is required for equilibrium stability?

Answer 12

• This equlibrium is not stable unless volumes are fixed as unequal particle distribution occurs

Question 13

How are the Gibbs Donnan equlibria and RMP difference?

Answer 13

◦ The Donnan equlibrium is a completely passive process: i.e. no active transporters are involved in maintaining this equilibrium.
◦ A Donnan equilibrium is an equilibrium, i.e. ion concentrations on either side of the barrier are static.
◦ If the Donnan equilibrium were to become fully established, the increase in intracellular ions would cause cells to swell due to the osmotic influx of water.
◦ At a Donnan equilibrium, the resting membrane potential would be only about -20 mV. This potential would exist even if the membrane permeability for all ions was the same.
◦ The resting membrane potential, in contrast, requires different permeabilities for potassium and for sodium, and is maintained actively by constant Na+/K+ ATPase activity.
◦ Because biological membranes (especially of exciteable tissues) are never at equilibrium, the Goldman-Hodgkin-Katz equation is usually a better choice for explaining their electrochemical behaviour.

Question 14

Draw a mitochondrion

Answer 14

Question 15

Explain the two membranes of a mitochondria
- permeabiliuty
- electical or chemical gradients across the membrane
- significant anatomical features
- Transmembrane channels

Answer 15

◦ Outer membrane with pores - porous lipid bilayer permit relatively unobstructed movement of molecules in either direction. Porins are called VDACs (voltage gated anion channels) - no electrochemical rgadient or potential different across this
◦ Inner membrane lipid bilayer more impermeable than cell membrane without pores - folded up to increase surface area - cristae mitochondriales are the invaginations
‣ Separated from the rest of the intermembranous space by semipermeable junctions creating intercristal space
‣ Filled with fluid rich in hydrogen ions via electron transport chain which is imbedded in the internal membrane - the cristae junctions stop this spilling into cystol but this creates a -200mV value between the intercristal space and the matrix
◦ These membranes meet at contact sites (areas where membrane lipids and proteins may be exchanged with other organelles)

Question 16

What are the 4 major structural features of a mitochondrion matrix

Answer 16

◦ ATP synthase molecules on the inner surface of the inner membrane
◦ Mitochondrial ribosomes in the inner compartment
◦ Mitochondrial DNA in the inner compartment
◦ Electron dense-granules in the inner compartment (composed of RNA)

Question 17

Mitochondrial DNA is unique because?

Answer 17

• Maternal inheritance from oocyte mitochondrial DNA (paternal contribution is minimal)
• Mitochondrial DNA is short (16,500 base pairs) and encodes only 8 protein subunits (mainly from the electron transport chain) - but host nucleus also contributes to ETC enzymes
  ◦ polypoind - 10 identical copies of the same DNA molecule, circular structure
• This DNA is susceptible to mutation (10 times more than nuclear DNA)
• Mitochondria are motile and self replicating

Question 18

What are the function of a mitochondria (4 domains)

Answer 18

• ATP synthesis functions, including:
  ◦ Citric acid cycle
  ◦ Electron transport chain
  ◦ Beta-oxidation of long chain fatty acids
• Regulatory and synthetic functions
  ◦ Haem synthesis
  ◦ Calcium ion storage
  ◦ Urea cycle
  ◦ Haem synthesis
  ◦ Steroid synthesis
• As a byproduct of these functions
  ◦ Heat production
  ◦ CO2 production
  ◦ Production of reactive oxygen species
• Non-metabolic roles
  ◦ Apoptosis

Question 19

Regulatory and syntheetic functions of a mitochondria?

Answer 19

• ATP synthesis functions, including:
  ◦ Citric acid cycle
  ◦ Electron transport chain
  ◦ Beta-oxidation of long chain fatty acids
• Regulatory and synthetic functions
  ◦ Haem synthesis
  ◦ Calcium ion storage
  ◦ Urea cycle
  ◦ Haem synthesis
  ◦ Steroid synthesis
• As a byproduct of these functions
  ◦ Heat production
  ◦ CO2 production
  ◦ Production of reactive oxygen species
• Non-metabolic roles
  ◦ Apoptosis

Question 20

Byproducts of the ATP and regualtory functions?

Answer 20

• ATP synthesis functions, including:
  ◦ Citric acid cycle
  ◦ Electron transport chain
  ◦ Beta-oxidation of long chain fatty acids
• Regulatory and synthetic functions
  ◦ Haem synthesis
  ◦ Calcium ion storage
  ◦ Urea cycle
  ◦ Haem synthesis
  ◦ Steroid synthesis
• As a byproduct of these functions
  ◦ Heat production
  ◦ CO2 production
  ◦ Production of reactive oxygen species
• Non-metabolic roles
  ◦ Apoptosis

Question 21

Non metabolic roles of mitochondria 1

Answer 21

• ATP synthesis functions, including:
  ◦ Citric acid cycle
  ◦ Electron transport chain
  ◦ Beta-oxidation of long chain fatty acids
• Regulatory and synthetic functions
  ◦ Haem synthesis
  ◦ Calcium ion storage
  ◦ Urea cycle
  ◦ Haem synthesis
  ◦ Steroid synthesis
• As a byproduct of these functions
  ◦ Heat production
  ◦ CO2 production
  ◦ Production of reactive oxygen species
• Non-metabolic roles
  ◦ Apoptosis

Question 22

Metabolic roles of mitochondria 3

Answer 22

• ATP synthesis functions, including:
  ◦ Citric acid cycle
  ◦ Electron transport chain
  ◦ Beta-oxidation of long chain fatty acids
• Regulatory and synthetic functions
  ◦ Haem synthesis
  ◦ Calcium ion storage
  ◦ Urea cycle
  ◦ Haem synthesis
  ◦ Steroid synthesis
• As a byproduct of these functions
  ◦ Heat production
  ◦ CO2 production
  ◦ Production of reactive oxygen species
• Non-metabolic roles
  ◦ Apoptosis

Question 23

Regulatory and sythentic functions

Answer 23

• ATP synthesis functions, including:
  ◦ Citric acid cycle
  ◦ Electron transport chain
  ◦ Beta-oxidation of long chain fatty acids
• Regulatory and synthetic functions
  ◦ Haem synthesis
  ◦ Calcium ion storage
  ◦ Urea cycle
  ◦ Haem synthesis
  ◦ Steroid synthesis
• As a byproduct of these functions
  ◦ Heat production
  ◦ CO2 production
  ◦ Production of reactive oxygen species
• Non-metabolic roles
  ◦ Apoptosis

Question 24

Where does beta oxidation occur

Answer 24

Mitochondrial mtrix

Question 25

Where is acetyl CoA created form pyruvate

Answer 25

mitochondrial matrix

Question 26

Where does the Kreb’s cycle take place

Answer 26

mitochondrial matrix

Question 27

Where does the ETC occur

Answer 27

inner membrane between mitochondrial matrix and mitochondrial intermembranous space

Question 28

Urea cycle occurs where

Answer 28

mostly occurs in the cytosol (begins and ends) but detour through the mitochrondium

Question 29

How much glucose energy is lost as heat?

Answer 29

60%

Question 30

Why is so much energy lost in glucose metabolism to energy?

Answer 30

H+ leak at the ETC
Substrate oxidation is exothermic

Question 31

What 3 main mechanisms of diffusion are there?

Answer 31

◦ Passive (“simple”) diffusion: occurs along a concentration gradient directly through the lipid bilayer. Example: Oxygen and carbon dioxide molecules.
◦ Facilitated diffusion: occurs along a concentration gradient, but requires a protein channel as a conduit. Example: aquaporins
◦ Ion channels: selective conduit proteins, usually gated, which only allow the passage of specific ions, usually in response to a triggering stimulus. Example: voltage-gated sodium channels.

Question 32

What active transport mechanisms are there?

Answer 32

◦ Primary active transport: mediated by a “pump” protein which uses chemical energy stored in ATP to facilitate the transport of molecules (usually against their concentration gradient). Example: sodium and potassium transport by Na+/K+ ATPase.
◦ Secondary active transport: mediated by an exchaner or co-transporter which facilitates the movement of molecules using the energy of a concentration gradient set up by another (primary) ATP-powered transport process. Example: sodium and glucose co-transport.

Question 33

Vesicle transport across cell membranes is called (2)? examples

Answer 33

◦ Endocytosis: where the transport of substances into the cell occurs by formation membrane-bounded vesicles containing the substance. Example: catecholamine neurotransmitter reuptake.
◦ Exocytosis: the opposite of endocytosis, where vesicles transport molecules to the cell surface and empty their contents into the extracellular fluid. Example: catecholamine neurotransmitter release.

Question 34

How thick is a cell membrane

Answer 34

5nm

Question 35

What is the structure of a cell membrane?

Answer 35

◦ Phospholipid bilayer with embedded proteins, 5 nm thick
◦ Bilayer is formed by amphipathic molecules (phosphate-rich “heads” hydrophilic on the outside and hydrophobic lipid “tails” on the inside
◦ negative surface charge leading to adsorbed cations

Question 36

What charge is a cell membrane

Answer 36

negative

Question 37

Composition of cell membrane (5)

Answer 37

◦ Lipids (50% by weight)
‣ ​​​​​​Outer membrane: phosphatidylcholine and sphingomyelin
‣ Inner membrane: phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol
‣ Variable amounts of cholesterol
◦ Proteins (50% by weight)
‣ Integral proteins (transmembrane proteins and lipid-anchored proteins which are confined to only one side of the membrane)
‣ Peripheral proteins (surface)
◦ Polysaccharides
‣ Glycosylated components of glycolipids and glycoproteins
‣ These form the cellular glycocalyx
◦ Water
‣ ​​​​​​​Present between lipid molecules in a highly organised form, as well as bulk water in pores and channels
◦ Ions
‣ ​​​​​​​Adsorbed ions (eg. calcium, sodium)
‣ Attracted to the membrane by the intrinsic negative charge of the phospholipid heads

Question 38

What sort of lipids are in the cell membrane

Answer 38

◦ Lipids (50% by weight)
‣ ​​​​​​Outer membrane: phosphatidylcholine and sphingomyelin
‣ Inner membrane: phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol
‣ Variable amounts of cholesterol

Question 39

What is the main function of the cell membrane? How good at it is it? How is it regulated?

Answer 39

◦ Lipid bilayer membranes have limited water permeability, about 1μm/s
◦ Total water movement between intracellular and extracellular fluid compartments is still relatively rapid, as the total membrane surface is very thin and has a vast surface area
◦ Membrane permeability to water differs between cells, because of the presence of embedded proteins and lipids which change the membrane properties (eg. aquaporins, or lipid rafts)
◦ The range of permeabilities can span from almost zero (no permeability whatsoever, eg. bladder urothelium) to 600 µm/s (collecting duct in the absence of vasopressin)
◦ The main mechanism that determines the balance of volume between the intracellular and extracellular compartments is the equilibrium of osmolality between these compartments
◦ The most important osmotic agent which contributes to this equilibrium is extracellular sodium (86% of osmolality of ECF), mainly because it is under tight homeostatic control
◦ Over longer timeframes (days), the intracellular osmolality can also be adjusted by intracellular generation of idiogenic osmoles.

Question 40

What is a neurons resting membrane potential?

Answer 40

• Neruons -70mV

Question 41

What is an average cells resting membrane potential

Answer 41

-90mV

Question 42

What is skeletal muscle resting membrane potential

Answer 42

-80mV

Question 43

Smooth muscle celll RMP

Answer 43

-55mV

Question 44

Cardiac cells RMP

Answer 44

• Cardiac muscle -80mV; Purkenje fibres -90mV, AV nodal cell -65mV

Question 45

How is K pivotal to the RMP

Answer 45

35:1 ratio intra to extracellular
The membrane is selectively permeable to most ions, potassium is the most permeable

• Electrical gradients are generated because potassium leak (via K2P channels) from the intracellular fluid creates a negative intracellular charge. This charge attracts potassium ions back into the cell and thus opposes the chemical gradient.

Question 46

The Nernst equation solved for
- K
- Na
- Cl
- Ca

Answer 46

• The Nernst potential for each ion is the transmembrane potential difference generated when that ion is at electrochemical equilibrium
  ◦ –> K solved for baseline gives a potential difference of -94mV; Na +60mV, Ca +130mV, Cl -80mV

Question 47

What does the Goldman Hodgkin Katz equation take into account

Answer 47

◦ Factoring - valence, polarity of charge, differing concentrations on inside and outside and membrane permeabilities

Question 48

What is the Goldman Hodgkin Katz equation

Answer 48

Simplified = -60mV log (10) K in/Kout

Question 49

What role does Na/K ATPase have in RMP

Answer 49

Minor role
Contributing takes RMP from -86 to -90mV

Question 50

Types of cell signalling 4

Answer 50

Autocrine signalling: transmitter excreted into the extracellular fluid return to bind surface receptors of the same cell.
(example: in lung adenocarcinoma cells IL-6 is an autocrine growth promoter)
Juxtacrine signalling: the signalling molecules are anchored in the cell membrane of one cell, and bind to receptors on the surface of immediately neighbouring cells (example: TGFα signalling in epidermal cells at the edges of wounds)
Synaptic signalling: transmitters are released at synaptic junctions from nerve cells and act across a narrow synaptic cleft on a postsynaptic cell.
(example: serotonin, dopamine, acetylecholine)
Paracrine signalling: transmitters diffuse in the extracellular fluid to affect neighbouring cells that may be some distance away.
(example: fibroblast growth factor (FGF) family involved in embryological limb development)
Endocrine signalling: transmitters reach distant cell targets via the circulating body fluids, mainly blood.

Question 51

Intracellular fluid distirbution
- What % is water
Where is that water distirbuted?

Answer 51

• Intracellular fluid volume is:
  ◦ 50% organelles + 50% water volume
  ◦ Approximately 20-30% non-diffusible macromolecules/proteins
  ‣ Muscle cells 23%
  ‣ Erythrocytes 35%
  ◦ Approximately 70-80% water
  ‣ Of this water, a variable fraction (10-70%) is available as liquid water solvent
  ‣ The rest is sequestered as a hydrating molecular layer adsorbed onto the surface of the larger molecules - in the free spaces in between proteins it is adsorbed onto the protein surface
  ◦ The liquid fraction of the water is mobile and its movement is the main source of changes in cell volume

Question 52

Intracellular ions are distributed how?

Answer 52

◦ Ions in the intracellular fluid are adsorbed onto macromolecules and have decreased diffusional mobility (perhaps 15% of what might be expected from free solution)

Question 53

Average intracellualr concentration of - Na

Answer 53

‣ Na+ 10-30 mmol/L
‣ K+ 130-150 mmol/L
‣ Mg2+ 10-20 mmol/L
‣ Ca2+ close to 0 mmol/L
‣ Cl- 10-20mmol/L
‣ PO4-100-130mmol/L

Question 54

Average intracellular concnetration of K

Answer 54

‣ Na+ 10-30 mmol/L
‣ K+ 130-150 mmol/L
‣ Mg2+ 10-20 mmol/L
‣ Ca2+ close to 0 mmol/L
‣ Cl- 10-20mmol/L
‣ PO4-100-130mmol/L

Question 55

Average intracellula concnetration of Mg

Answer 55

‣ Na+ 10-30 mmol/L
‣ K+ 130-150 mmol/L
‣ Mg2+ 10-20 mmol/L
‣ Ca2+ close to 0 mmol/L
‣ Cl- 10-20mmol/L
‣ PO4-100-130mmol/L

Question 56

Average intracellular concentration of Ca

Answer 56

‣ Na+ 10-30 mmol/L
‣ K+ 130-150 mmol/L
‣ Mg2+ 10-20 mmol/L
‣ Ca2+ close to 0 mmol/L
‣ Cl- 10-20mmol/L
‣ PO4-100-130mmol/L

Question 57

Average intracellular concentration of Cl

Answer 57

‣ Na+ 10-30 mmol/L
‣ K+ 130-150 mmol/L
‣ Mg2+ 10-20 mmol/L
‣ Ca2+ close to 0 mmol/L
‣ Cl- 10-20mmol/L
‣ PO4-100-130mmol/L

Question 58

Average intracellular concentration of PO4

Answer 58

‣ Na+ 10-30 mmol/L
‣ K+ 130-150 mmol/L
‣ Mg2+ 10-20 mmol/L
‣ Ca2+ close to 0 mmol/L
‣ Cl- 10-20mmol/L
‣ PO4-100-130mmol/L

Question 59

pH in cells

Answer 59

6-7.5

Question 60

How is intracellular volume regulated

Answer 60

◦ The first Gibbs-Donnan effect which is established by the equilibration of diffusible and non-diffusible solutes on either side of the cell membrane
‣ Diffusable solutes are mainly ions, and they can traffic relatively freely.
‣ Non-diffusable solutes are mainly macromolecules such as proteins, and they are trapped on their side of the membrane.
‣ First passive Gibbs Doonan effect is due to protein - equilibrium of diffusible ions proudces an osmotic gradient sucking water into cells
◦ The second Gibbs-Donnan effect which is maintained by the actions of Na+/K+ ATPase
‣ keeps intracellular osmolality equal to extracellular osmoallity by constant flow of Na out fo thec ell

Question 61

How can there be two Gibbs Donnan effects

Answer 61

◦ The first Gibbs-Donnan effect which is established by the equilibration of diffusible and non-diffusible solutes on either side of the cell membrane
‣ Diffusable solutes are mainly ions, and they can traffic relatively freely.
‣ Non-diffusable solutes are mainly macromolecules such as proteins, and they are trapped on their side of the membrane.
‣ First passive Gibbs Doonan effect is due to protein - equilibrium of diffusible ions proudces an osmotic gradient sucking water into cells
◦ The second Gibbs-Donnan effect which is maintained by the actions of Na+/K+ ATPase
‣ keeps intracellular osmolality equal to extracellular osmoallity by constant flow of Na out fo thec ell

Question 62

Factors which determine the equlibiria of the two gibbs donnan effects intracellualr? 4

Answer 62

◦ Activity of Na+/K+ ATPase - maintains the second Gibbs Doonan equation
◦ Extracellular solute concentration - they factor into the Gibbs Doonan effects - the main solute being sodium as it and its anions contribute 85% of the total extracellular fluid osmolality
‣ Can be modified
* Hypertonic saline/mannitol to decrease CNS cells size
* Removing urea from ECF leading to dialysis disequilibrium syndrome
* Overly rapid correction of elevated BSL in HHS –> cerebral oedema
◦ Intracellular ion concentration - diffusable solute concentrations via Gibbs Doonan equation
‣ Cannot be directly controlled –> see the cellular responses to changes in tonicity below
◦ Intracellular macromolecule concentration
‣ Idiogenic osmols - organic non diffusable molecules can be synthesied or degraded e.g. sugar alcohols, amino acids - 2-7 days to do
* Cells can respond to hypotonia faster than they can to hypertonia (takes longer to synthesies than degrade)

Question 63

What is the Gibbs Donnan effect

Answer 63

describes the unequal distribution of permeant charged ions on either side of a semipermeable membrane which occurs in the presence of impermeant charged ions.

Question 64

In the Gibbs Donnan equation each solution on each side of the mmebrane has qhat characteristics

Answer 64

Each solution is electrically neutral

The product of diffusible ions on one side of the membrane will be equal to the product of diffusible ions on the other side of the membrane
‣ e.g. {K+}intracellular x {Cl-} intracellualr = [K+] extracellular x [Cl-] extracellular

Question 65

Is the Donnan equilibrium a passive or active process

Answer 65

◦ The Donnan equlibrium is a completely passive process: i.e. no active transporters are involved in maintaining this equilibrium.
◦ A Donnan equilibrium is an equilibrium, i.e. ion concentrations on either side of the barrier are static.

Question 66

If the Donnan equilibrium occured for cells what would occur? Therefore what better represents what actually occurs?

Answer 66

◦ If the Donnan equilibrium were to become fully established, the increase in intracellular ions would cause cells to swell due to the osmotic influx of water.
◦ At a Donnan equilibrium, the resting membrane potential would be only about -20 mV. This potential would exist even if the membrane permeability for all ions was the same.
◦ The resting membrane potential, in contrast, requires different permeabilities for potassium and for sodium, and is maintained actively by constant Na+/K+ ATPase activity.
◦ Because biological membranes (especially of exciteable tissues) are never at equilibrium, the Goldman-Hodgkin-Katz equation is usually a better choice for explaining their electrochemical behaviour

Question 67

Describe the structure of the Na/K ATPase pump - size, molecular mass, member of what family, subunit no. most important of which is

Answer 67

◦ The Na+/K+ ATPase pump is a heteromeric transmembrane protein with a total molecular mass of around 170 kDa.
◦ It is a member of the P-type ATPase family of ion pumps, all of which form a covalently bound aspartylphosphate using ATP to move their specific ions, and which are ubiquitous to all forms of eukaryotic and prokaryotic life (Møller et al, 1996).
◦ The complex contains three subunits (one α, one β, and one FXYD subunit)
◦ The α subunit is the main actor and contains the cytoplasmic domains necessary for function

Question 68

Function of Na/K ATPase - how does it perform its function

Answer 68

◦ The pump cycles through two states, the sodium-affinity state (E1) and the potassium affinity state (E2)
◦ In the E1 state, three high affinity sites on the cytoplasmic domain binds three sodium atoms (they are attracted to negative charges on aspartate and glutamate residues)
◦ This blocks the cytoplasmic pore because the cytoplasmic domain undergoes a conformational change
◦ Now, the pump binds ATP and is phosphorylated.
◦ The release of the ADP left over from this process triggers the change to the E2 state, where the pump loses its affinity for sodium and gains an affinity for potassium
◦ The sodium atoms are therefore released from their binding sites, via the extracellular domain.
◦ The extracellular domain in the E2 state has a high affinity for potassium ions and binds two of them
◦ This binding then closes the extracellular domain
◦ The protein is phosphorylated after this, and changes back to the E1 state, where its affinity for potassium is reduced (and the potassium is released via the cytoplasmic domain, which remains open and ready to accept sodium ions

Question 69

Why might a cells size change?

Answer 69

• Challenges to intracellular volume and fluid composition include:
  ◦ Energy dependence, even where extracellular fluid is isoosmotic
  ◦ Changes in extracellular fluid osmolality
  ◦ Changes in extracellular fluid ion concentration
  ‣ Hyperkalemia: cell membranes are relatively permeable to potassium, and extracellular increases often result in intracellular increases. Cells will swell as the consequence.
  ‣ Metabolic acidosis: organic acids may enter cells, contribute to intracellular acidosis, and increase intracellular sodium uptake by the Na+/H+ exchanger which alkalinises the cell in return for increased intracellular osmolality. Again, cells will swell.
  ◦ Influence of hormones which affect cellular regulatory mechanisms

Question 70

IN response to extracellular hypertonia what do cels do?

Answer 70

◦ Acutely, cells accumulate potassium and chloride
‣ Absorb more sodium into the cell via Na+-K+-2Cl- cotransporter
‣ Absorb more sodium into the cell via a Na+/H+ exchanger
‣ Exchange the sodium for potassium using Na+/K+ ATPase
‣ Absorb more chloride into the cell via Cl-/HCO3- exchanger
‣ The net effect is potassium and chloride gain –> voluem gain
◦ Chronically, cells accumulate “idiogenic osmoles” which take some time to produce

Question 71

In response to extracellular hypotonia what do cells do?

Answer 71

◦ Acutely, cells excrete potassium and chloride
‣ This can be independent, as co-transport, or as a part of a parallel K+/H+ and Cl-/HCO3- exchange
◦ Acutely, cells release osmotically active organic solutes (“idiogenic osmoles”)

Question 72

What are idiogenic osmoles?

Answer 72

• Idiogenic osmoles:
  ◦ These are intracellular organic molecules, eg. sorbitol, inositol, glycine
  ◦ They are released from the cell in response to osmotic cell swelling, and synthesised in response to cell shrinking

Question 73

How does ischameia cause cellular swelling?

Answer 73

How ischaemia leads to cellular swelling
In short, the cells, when confronted with a loss of high energy phosphates, cannot maintain sodium efflux. The influx of sodium remains the same, or it may even increase because the intracellular fluid pH tends to drop in ischaemia and there is this annoying Na+/H+ exchanger which allows more sodium into the cell (inhibiting this protein appears to protect myocytes from ischaemia). As the cell membrane depolarises due to loss of electrochemical gradient, voltage-gated sodium channels also open.

Question 74

Structure and function of endoplasmic reticulum

Answer 74

• Endoplasmic reticulum:
  ◦ Structure
  ‣ 3D mesh of tubular structures and sheets
  ‣ All throughout the cytosol
  ‣ “Rough” ER is covered in ribosomes, whereas “smooth” ER is not.
  * Rough endoplasmic reticulum found in sites with extensive protein synthesis
  * Smooth endoplasmic reticulum dominant when hydrophobic sybstances and steriods are the primary thing synthesised
  ◦ Function
  ‣ Folding and modification of proteins
  ‣ Protein transport where their diffusion would otherwise be challenging
  ‣ Synthesis of phospholipids and steroids
  ‣ Storage of calcium ions in the ER lumen (sarcoplasmic reticulum)

Question 75

Structure and function of the golgi apparatus

Answer 75

◦ Structure:
‣ Stacked membraeous cisternae which shed vescicles for transport
* Cis face: the area which usually interfaces with the endoplasmic reticulum
* Cisternae, the hollow components of the apparatus wherein lipid or protein products are combined or concentrated
* Trans face: the area which produces a constant stream of vesicles containing finished product
* Vesicles: for transport to their destination
◦ Function:
‣ Post-translation modification of proteins, including glycosylation, phosphorylation and polymerisation
‣ Prepare proteins for exocytosis
‣ Synthesis of glycolipids and sphingomyelin

Question 76

Structure and function fo the nucleus

Answer 76

◦ Structure
‣ Outer nuclear membrane continuous with endoplasmic reticulum
‣ Inner nuclear membrane with nuclear pores - wraps nucleoplasm containing pores
‣ Nucleoplasm separated into heterochromatin and euchromatin
* Heterochromatin - condensed chromatin bulk of genetic material
* Euchromatin - disperesed chromatin
‣ A nucleolus where RNA and ribosomes are created
◦ Function
‣ Concentrates and maintains the genetic contents of the cell, which include the regulation of gene expression and replication.

Question 77

Structure and function of the mitochondria

Answer 77

◦ Structure
‣ Outer membrane with pores and inner membrane without pores
‣ Two separate compartments: intermembrane space or “outer compartment” and matrix space or inner compartment
‣ Organisation of the inner membrane into cristae (a comb of many folds) which increases its surface area
◦ Function
‣ ATP synthesis functions, eg. oxidative phosphorylation
‣ Regulatory and synthetic functions (eg, haem synthesis, calcium ion storage, urea cycle, haem and steroid synthesis)
‣ Heat production
‣ CO2 production
‣ Production of reactive oxygen species
‣ Apoptosis

Question 78

What is a lysosome? What is its function

Answer 78

◦ Structure
‣ Membrane-bound compartment in the cell, the last member of the endocytic pathway - equivalent to vacuoles of protozoa
‣ Usually have acidic internal pH and contain degradative enzymes
◦ Function
‣ Terminal destination for endocytosed material
‣ main function is degradation and catabolism