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Membrane Transport And Cell Signalling > Membrane Transport > Flashcards

Membrane Transport Flashcards

1
Q

Describe endocytosis

A

Membrane wraps around the molecule and brings it into the cells

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2
Q

Why is clathrin important in endocytosis

A

Aggravates aand binds to membrane
Forces it to bend inwards and pinch off

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3
Q

Describe exocytosis

A

Vesicles fuse with the membrane and releases its contents

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4
Q

Why is clathrin important in exocytosis

A

Hen it binds it opens up the vesicle

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5
Q

Describe the permeability of the phospholipid bilayer

A

High permeability to gases and steroids
Low permeability to ions

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6
Q

What determines the resting membrane potential

A

The distribution of ions across the membrane

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7
Q

What can oppose the movement of ins across the membrane

A

A charge difference

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8
Q

What is the importance of the Nernst equation

A

Predicts the equilibrium potential of conc gradient across membrane

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9
Q

What is the Nernst potential

A

No net movement of ions as net charge and conc are in equilibrium

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10
Q

Why is the Goldman-Hodgkin-Katz equation better than the Nernst equation

A

It takes into account all the ions and their respective permeabilities

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11
Q

How is resting membrane potential generated

A

The asymmetrical distribution of ion especially Na+ and K+
The differential permeability of the membrane to the ions

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12
Q

Why is the resting potential closer to the Nernst value for K+

A

Membrane more permeable to K+ due to having more K+ leaky channels

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13
Q

Whats the permeability ratio of K+:Na+ in non excitable cells

A

2:1

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14
Q

What is the voltage clamp used for

A

To allow for detailed measurements and analysis of electrical activity across the tissue

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15
Q

How does the voltage clamp work

A

Apply and change the voltage in increments
Record the effect on ion channel currents

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16
Q

What does measuring the current in a voltage clamp show

A

The total ionic current flowing through the membrane

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17
Q

Describe how a patch clamp works

A

Recording pipettes isolate a patch of membrane on the cell surface
Measures current flow through a single ion channel

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18
Q

What is a gigaseal

A

High resistance seal between membrane and micropipette created by suction

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19
Q

Why is a gigaseal important

A

Minimises background noise that can swamp the single channel currents

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20
Q

What are the 2 types of secondary transporters

A

Co transporters i.e symporters
Counter transporter i.e antiporters

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21
Q

How does a symporter work

A

Couples movement of a solute w movement of another’s down its conc gradient

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22
Q

How do antiporters work

A

couples movement of 2 or more solutes in opposite directions

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23
Q

What is the equation for flux

A

Flux = permeability x conc difference

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24
Q

Describe the flux at equilibrium

A

Inward flux = outward flux
Net flux = 0

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25
Q

What is the equation for permeability

A

Permeability = diffusion coefficient x partition coefficient /distance

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26
Q

What does the diffusion coefficient measure

A

The size of the diffusion area at a give time point

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27
Q

What does the partition coefficient measure

A

How easily a substance crosses the membrane

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28
Q

What are the 3 types of transporters that facilitate diffusion

A

Channels
Gated channels
Uniporters

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29
Q

Why’s is there a greater rate of flux at lower [solute]

A

Less solute flowing through so channels are not fully saturated

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30
Q

How do P-type ATPases work

A

Use phosphorylation of ATP to move substrate from low to high conc

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31
Q

Describe the structure of Na+/K+ pumps

A

Has 10 transmembrane domains and 3 cation binding domains

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32
Q

What domains are involved in regulation in Na+/K+ pumps

A

Nucleotide, phosphorylation and actuator

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33
Q

Why is there a 3:2 stoichiometry for Na+/K+ pumps

A

Na+ fits into the domain easier as K+ is larger

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34
Q

What can inhibit Na/K+ pumps

A

Ouabain and cardiac glycosides

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35
Q

What is the Gibbs-Donnan effect

A

Describes the unequal distribution of ions on either side of the membrane in the presence of other ions that can’t cross the membrane

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36
Q

What is the impact of negatively charged molecules on the electrical activity of the cell

A

Largely try and hold onto the positive ions that try and leave the cell

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37
Q

How does the Na+/K+ pump raise the water potential in the cell

A

Removes some of the dissolved solutes
Less driving force for the water to come in

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38
Q

What are ATP binding cassette (ABC) transporters

A

Channels that transport small molecules

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39
Q

What increases the probability of ABC transporters opening

A

Presence of ATP in the NBD domain
Phosphorylation of R domain

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40
Q

What are the 2 different membrane spanning domains that ABC transporters have

A

Nucleotide binding domain NBD
Regulatory domain R

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41
Q

How is the CFTR an atypical ABC transporter

A

ATP regulates the channels
It binds to the R domain not just to the NBDs

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42
Q

What is osmolarity

A

The total conc of dissolved particles in a litre solution

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43
Q

What is osmolality

A

The number of dissolved particles per unit mass

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44
Q

What is osmotic pressure

A

Pressure exerted by flow of water across membrane determined by solute conc

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45
Q

What is tonicity

A

Measure of the effect of a solution has on cells placed in it
Driven by osmolarity

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46
Q

What is the equation for water flow

A

Water flow = hydraulic water permeability x change in pressure

47
Q

What is the movement of a solute dependent on

A

The change in concentration
Concentration difference and the water flow

48
Q

What is osmotic pressure

A

The pressure applied to a system to perfectly balance the flow of water across the membrane

49
Q

What does it eat if the solute coefficient equals 1

A

Membrane is impermeable to the solute

50
Q

What does it eat if the solute coefficient equals 0

A

Membrane is fully permeable

51
Q

What does it eat if the solute coefficient equals 0.5

A

The membrane is partially permeable

52
Q

What hormone increase transcription of aquaporins

A

Vasopressin

53
Q

Why is there a high proliferation rate in epithelial cells

A

Resit a lot of damage and therefore are prone to cancer

54
Q

Describe the structure of epithelial cells

A

Sheet like structures that line external and internal structures

55
Q

What are the protective epithelial cells

A

Simple columnar and stratified squamous

56
Q

What epithelial cells are involved in secretion and absorption

A

Simple squamous and simple cuboidal

57
Q

What epithelial cell is stretchy

A

psudeostratified squamous

58
Q

What are tight junctions

A

Membrane proteins that bind adjacent epithelial cells

59
Q

What is the function of tight junctions

A

Form a physical barrier to separate the baso lateral and apical sides

60
Q

How are tight junctions useful for absorption and secretion

A

Create a polarity across the cell
Cell can express different transporters on different sides of the cell

61
Q

What molecules form a tight junction

A

Claudin and occludin

62
Q

What happens if there is low resistance in tight junctions

A

Leaky junctions - daily secrets and absorbs

63
Q

What molecule causes leaky junctions

A

Claudin 2

64
Q

What are anchoring junctions

A

Proteins that anchor to the basal lamina and neighbouring cells
Forms cohesive unit for stability

65
Q

Why are gap junctions important

A

Allow neighbouring cells the share the same intracellular environment
Important for cell signalling

66
Q

What os the basement membrane

A

Basal lamina + reticular laminate

67
Q

What is the importance of basal lamina

A

Strong flexible foundation
Allows cell to root to something

68
Q

What is the first step in NaCl absorption

A

Passive facilitated entry of Na+ across apical lumen membrane
Through Na+ channels

69
Q

What is the send step in NaCl absorption

A

Active exit of Na+ across the basolateral membrane

70
Q

What is the third step of NaCl absorption

A

Paracellular diffusion of Cl- through tight junctions

71
Q

What is the last step in NaCl- absorption

A

Absorption of water that is osmotically driven

72
Q

What is ENaC

A

Major sodium epithelial channel

73
Q

What is the function of ENaC in the lungs

A

To control the amount of airway surface fluid and alveolar lining fluid

74
Q

What is the function of ENaC in the kidneys

A

Controls whole body [Na+] and blood pressure therefore blood volume

75
Q

What is the function of ENaC in the sweat glands

A

Na+ retention/reabsorption by sweat ducts to produce hypotonic sweat

76
Q

What is the structure of ENaC

A

3 functional subunits; alpha, beta and gamma
2 transmembrane domains per subunit
Each subunit has a large loops that stick out of the luminal side

77
Q

What is necessary for a functional ENaC

A

All 3 subunits - constituency active but regulated

78
Q

What forms the pore of ENaC

A

The trans membrane domains of the subunits

79
Q

What inhibits EnaC

A

Amiloride

80
Q

What is the importance of the loops on hte subunits

A

Site of proteases (CAP) that crave the loops to increase activity

81
Q

What is the importance of SPLUNC1 when bound to ENaC

A

Binds to beta ENaC to protect regulation

82
Q

What is the ENaC expressed by in the nephron

A

Aldosterone sensitive distal nephron (ASDN)

83
Q

What is the importance of ENaCs in ASDN

A

Determine final urine salt composition through aldosterone

84
Q

What happens if the salt intake is low

A

Low blood vol -> aldosterone release -> increase Na+ reabsorption -> increases blood vol

85
Q

How does aldosterone stimulate Na+ absorption through ENaC

A

Via principle cells in the ASDN

86
Q

What does aldosterone bind to in principle cells

A

Mineralcorticoid receptor R

87
Q

What does aldosterone increase

A

Surface ENaC levels
Na/K ATPase density
ATP supply
K+ secretion across apical membrane

88
Q

How does aldosterone lead to an increase in surface ENaC levels

A

Bind to mineralocorticoid receptor -> regulates the production of aldosterone regulatory proteins
Decreased rate of retrieval

89
Q

What regulates the retrieval of channels

A

Ubiquitination

90
Q

How is a ubiquitin group added to a lysine residue in ENaC

A

Nedd4-2 binds to P-Y motif in the C terminus of an ENaC subunit
Covalently adds a ubiquitin group

91
Q

How does aldosterone inhibit ubiquitination of ENaC

A

Stimulates serum and glucocorticoid regulated kinases (SGK1) which phosphorylates Nedd4-2
This allows 14-3-3 to bind to it which prevents Nedd4-2 binding to ENaC inhibiting ubiquitination

92
Q

What is hypertension

A

High blood pressure
Too much aldosterone which stimulates the creation of ENaC channels -> too much Na+ present

93
Q

What are the 2 types of Cl- channels

A

CTFR and calcium activated Cl- channel (CaCC)

94
Q

What regulates CTFR channel activity

A

Regulated by PKA and ATP

95
Q

What drives the accumulation of chloride in the cell

A

NKCC transporter on the baso lateral membrane
Utilise the pre existing Na+ gradient

96
Q

What happens if another ATP binds to site 2 on the CFTR after the pore closes

A

The channel will reopen a s ling as the RD is phosphorylated

97
Q

Where are CaCCs located

A

Apical membrane of most epithelial cells that express CFTR
Not intestinal cells

98
Q

What activates CaCCs

A

A rise in cytosolic Ca2+ and the activation is usually transient

99
Q

What are the 2 members of the TMEM16 family

A

TMEM16A and TMEM16B

100
Q

Where is TMEM16A found

A

Epithelial cells

101
Q

What allows the pore to open in TMEM16A

A

Ca2+ bind to glutamate residues in the alpha helices forcing them to move apart i.e opening the pore

102
Q

What are the mechanism of HCO3- secretion

A

Directly through the Cl- channel
Indirectly via coupling the Cl- channel (apical Cl/HCO3 exchanger)

103
Q

How does CFTR regulate the activity of SLC26A anion exchangers in epithelial cells

A

.cAMP/PKA activation of CFTR switches on AE
Requires interaction of 2 proteins added by CAP70 and CFTR RD phosphorylation

104
Q

What is the function of acinar cells

A

Produce a small amount of NaCl fluid fluid
Regulated through TMEM16A channels

105
Q

What is the function of duct cells

A

Produce a high volume of NaHCO3 rich secretion using both CFTR and SLC26A6

106
Q

Why do CF patients produce mucus in the digestive system

A

CFTR exchanges aren’t working
No secretion from ductal cells so digestive juices don’t travel = mucus build up

107
Q

Why are some CF patients pancreatic insufficient

A

Digestive enzymes begin digesting the exocrine pancreas due to the mucus build up

108
Q

Where does ENaC mediated fluid absorption happen in the digestive system

A

Only in the colon - other mechanisms in other part of the GI tract

109
Q

Describe the sodium linked absorptive ion transporter

A

Utilise PAT1 and DRA and couple to Na+/H+ exchanger on apical membrane
Combine H+ and HCO3- in the gut

110
Q

Describe how nutrient absorptive transporters work

A

Use glucose and other osmotically active solutes that are brung into the cell
Brings water into the cell

111
Q

What is the main cause of secretory diarrhoea

A

Dysregulation of fluid homeostasis due to dysregulation of cell signalling

112
Q

What is the mechanism that cholera inhibits absorption and stimulation of secretion

A

Causes ADP-ribosylation that blocks GTP hydrolysis making adenylyl cyclase permanently active
= over stimulation of CFTR and inhibition of NaCl absorption

113
Q

Describe oral rehydration therapy

A

Utilises nutrient absorptive transporters that bring in solutes allowing water to follow

Membrane Transport And Cell Signalling (4 decks)

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