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imms > Membrane Ultra-Structure And Function > Flashcards

Membrane Ultra-Structure And Function Flashcards

1
Q

Phospholipids are one of either:

A

Serine (phosphatidyl-serine)

Choline (phosphatidyl-choline)

Inositol (phosphatidyl-inositol)

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2
Q

Phospholipids are Made up of:

Functions of phospholipid bilayer:

A

Fatty acid tails

Phospholipids head

  • Main function of the cell membrane is to act as a selective barrier to the passage of molecules, allowing some molecules to cross whilst excluding others
  • Other major function is to act as a barrier to the outside environment and compartmentalise cells
  • The cell membrane is semipermeable; absorbs nutrients and expels waste AND maintains intracellular balance
  • Helps cell respond to signals i.e. receptors a located on cell membrane for peptide hormones to bind to
  • Has molecules on it for intercellular adhesion
  • Can act as an insulator i.e. myelin sheath
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3
Q

Fatty acid tails

A

Non-polar
Hydrophobic
Saturated and unsaturated bonds

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4
Q

Phospholipid Head

A

Polar (charged)
Hydrophillic

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5
Q

Phospholipid bilayer’s permeability

A

Fluidity modified by cholesterol and temperature

Freely permeable to
Water (aquaporins)
Gases
(CO2, N2, O2)
Small uncharged polar molecules
(Urea, ethanol)

Impermeable to…
Ions
(Na+, K+, Cl-, Ca2+ etc.)
Charged Polar molecules
(ATP, Glucose-6-phosphate)
Large uncharged polar molecules
(Glucose)

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6
Q

How do molecules cross the cell membrane?

A

Simple diffusion

Facilitated diffusion

Primary active transport

Secondary active transport

Ion channels

Pink-/phago-cytosis

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7
Q

Examples of simple diffusion

A

Blood gases, water
Urea, free fatty acids
Ketone bodies

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8
Q

Facilitated diffusion examples

A

Glucose (hexose sugars)
GLUT family

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9
Q

Primary active transport examples

A

Ions (Na+, K+, Ca2+, H+, HCO3-)
Water-soluble vitamins
Energy direct from ATP

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10
Q

Secondary active transport examples

A

Glucose (hexose sugars)
Symporters (Na+ + X)
Energy from ion gradient
Co-transport

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11
Q

Ion channels examples

A

Many sorts…
Voltage-gated
“Leak” channels

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12
Q

Pino-/phago-cytosis

A

Vesicles

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13
Q

Why are membranes and membrane proteins needed?

A

Cell polarisation
Compartmentalisation
Ionic gradients
Diffusion (Nernst potential)
Membrane potential

Tightly regulated
Disease disrupts this
Heart disease, kidney failure

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14
Q

What is the membrane potential (Em)?

A

Potential difference across the cell membrane generated by differential ion concentrations of key ions (K+, Na+, Ca2+, Cl-)

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15
Q

Membrane potential

A

Contributions from diffusion potential of each ion
(AKA Nernst or Equilibrium potential)
Permeability of each ion in a given membrane
K+ is the major determinant of Em
Stable in most cells (but sensitive to ionic imbalance)
Transient variability in excitable tissue
Ventricular myocytes Em ~ -90mV

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16
Q

Convection of membrane potential dictates:

A

Extracellular fluid potential = 0 mV (Reference)
Membrane potential is that on intra-cellular membrane
Composed of various individual diffusion potentials:
Ion+; Em has -ve value if diffusing from IC to EC (K+)
Ion+; Em has +ve value if diffusing from EC to IC (Na+ or Ca2+)
Ion-; Em has -ve value if diffusing from EC to IC (Cl-)

Collective ion diffusion potentials contribute to membrane potential

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17
Q

Nernst Equation

A

Slide 15

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18
Q

Ion conductance (permeability) is key determinant of Em

Permeability is dependant on:

A

Channel numbers
Channel gating
Change ion permeability lead to change Em

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19
Q

Kidneys and aldosterone:

A

Major role in K+ homeostasis
Renal failure
Conn’s Syndrome (too much aldosterone)

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20
Q

Increase in [K+]E (Clinically – hyperkalaemia):

A

Em less –ve (tending to depolarisation)
Reaches threshold more easily
Cell depolarisation more likely
Heart - decreased SAN firing / Bradycardia

Causes: renal failure, diuretics/ACE inhibitors, Addison’s, Acidosis.

Consequences: Risk of myocardial infarction since high potassium levels mess with resting potential generated in heart for heart contraction

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21
Q

Decreased [K+]E (Clinically – hypokalaemia):

A

Em more –ve (tending to hyperpolarisation)
Disrupts various K+ channels
Abnormal heart rhythms (arrhythmias)

Causes: diarrhoea, vomiting, alkalosis, hypomagnesaemia (low magnesium levels).

Consequences: weakness & cardiac dysrhythmia (abnormal heart beat - again since K is necessary for resting potentials and thus action potential generation etc.)

22
Q

Ischaemia

A

Hypoxia - decrease in [ATP]I
Opens KATP channel
EM less –ve (~-55mV) (4)
Depolarises easily
Fast Na+ channels inhibited ~ -55mV
Slow Ca2+-mediated depolarisation (0)
Early repolarisation (1); Decrease Plateau (2);
Lower Action potential duration (3,4; KATP?)

23
Q

Epithelia

A

Require polarisation of plasma membrane – apical vs basolateral surfaces
Permits cell-specific function – secretion/absorption
Strongly adhere to neighbours – tight junctions

24
Q

3 examples of epithelia

A

parietal cell (gastric pits)
intestinal epithelium
nephron

25
Q

Substrate movement across membranes occurs with movement of water…

A

Sodium:glucose co-transport (symport) - basis of Oral Rehydration Therapy…

26
Q

Epithelial cells in the nephron

A

Morphology and permeability of tubular epithelial cells changes along the tubule
Reflects specific function of each aspect of tubule:

27
Q

How do cells communicate using cell membrane receptors?

A

Signal Transduction

Internalise extra-cellular signal…
First message into second message

Many sorts

28
Q

Types of receptors found in nucleus- nucleus steroid receptors

A

Direct effect on gene expression
ER – tamoxifen
PR – mifepristone
AR – testosterone
GR – cortisol; dexamethasone
MR – aldosterone; spironolactone

29
Q

Signal transduction through ion channels

A

Ca 2+ - nifedipine
Na+ - Amiloride
K+ - Amiodarone

30
Q

Signal transduction through membrane-bound steroid receptors

A

In-direct effect on gene expression
E – cardiovascular effects?
P – uterine function/sperm function

31
Q

Signal transduction through neurotransmission

A

AchR – Muscarinic cholinergic blockade – atropine
GABA – benzodiazipines
Seretonin (5-HT3) - ondansatron

32
Q

Signal transduction through growth factors

A

EGFR – pertuzumab (Perjeta) – breast cancer
VEGF - bevacizumab (Avastin) – ovarian cancer
Growth Hormone – (Genetropin)
Insulin; IGFs

33
Q

6 parts of the G-Protein Coupled Receptors (GPCRs)

A

Receptor – gives primary specificity
Three G-proteins – a, b, g
Ga further specificity
Enzyme to modulate second messenger
(e.g. cAMP)
Enzyme to terminate signal
Phosphodiesterase

34
Q

GPCR

A

Ubiquitous (>800 sequences)
>50% of all drugs mimic or inhibit various GPCR
Significant drug target

35
Q

+ve; makes cAMP:

A

beta-2 agonists, PGE2 via EP2 receptor (uterine relaxation)
Intestinal epithelium
Cholera toxin – increased secretion

36
Q

-ve; prevents cAMP:,

A

alpha-2 adrenergic agonists - ergometrine
a, m, d, k, opioid receptors
PGE2 via EP1 and EP3 receptors (uterine contraction; Misoprostol)
M2 ACh receptors

37
Q

+ve; makes IP3 and DAG:

A

Oxytocin receptor, PGF2 via FP2a receptor
(uterine contraction; severe PPH; Carboprost)
M3 ACh receptors

38
Q

How does pH effect membrane function?

A

Both extremes damage the protein

Inhabits cell function

39
Q

Critical role for acid-base homeostasis

A

Plasma Ca2+

Cell membrane excitability/permeability

40
Q

Serum Calcium- 45% free ionised Ca2+

A

Biologically active
Change Ca2+ (active): Ca (inactive) ratio with no change in total calcium
Acidosis
less Ca2+ bound to plasma proteins (H+ ions buffered by albumin)
Alkalosis
more Ca2+ bound to plasma proteins (fewer H+ ions on protein)

Alkalotic patients more susceptible to hypocalcaemic tetany
Due to increased neuronal membrane Na+ permeability

41
Q

Serum calcium- 55% bound

A

Not biologically active
45% bound to albumin
10% anions – phosphate; lactate active form

42
Q

How does temperature effect membrane function?

A

Too cold – proteins slow down; membrane less fluid
Too hot – proteins denature; increased membrane fluidity. Can lead to heat exhaustion, heat stroke and dehydration

43
Q

Regulation of the SAN action potential- hypothermia

A

Lowers depolarization rate of cardiac pacemaker cells
Bradycardia (not vagally mediated)

Abnormal heart rhythms
Fibrillation (atrial and ventricle)

44
Q

Hypovolaemia and the Lethal triad

A

Diagram slide 35

45
Q

What is found in the phospholipid bilayer?

A

glycolipids: communication, joins cells to form tissues + stability

glycoproteins: for cell to cell recognition + acts as receptors

cholesterol: maintains fluidity in membrane

46
Q

Occluding

A

tight junctions help seal cells together in an epithelial sheet to prevent leakage of molecules between them

47
Q

Anchoring

A

ACTIN FILAMENTS

INTERMEDIATE FILAMENTS

HEMIDESMOSOMES

48
Q

Actin filaments

A

enable cell to cell adhesion through adherens
junctions

ADHERENS JUNCTION JOINS ACTIN BUNDLE IN ONE CELL TO A SIMILAR BUNDLE IN ANOTHER CELL - HELPS KEEP CELLS TOGETHER & cell to matrix (external to cell) adhesion through adherens junctions too

49
Q

Intermediate filaments

A

enable cell to cell adhesion through desmosomes (cell surface adhesion proteins + intracellular keratin cytoskeletal filaments - they resist shearing forces & JOIN THE INTERMEDIATE FILAMENTS IN ONE CELL TO THOSE IN A NEIGHBOUR) & cell to matrix adhesion through focal adheren junctions.

50
Q

Hemidesmosomes

A

anchor intermediate filaments in a cell to the basal lamina

51
Q

Communicating gap junctions

A

allows the passage of small water-soluble ions and
molecules

imms (29 decks)

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