Membrane Ultra-Structure And Function Flashcards by Sara Waheed

Phospholipids are one of either:

Serine (phosphatidyl-serine)

Choline (phosphatidyl-choline)

Inositol (phosphatidyl-inositol)

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Phospholipids are Made up of:

Functions of phospholipid bilayer:

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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Fatty acid tails

Non-polar
Hydrophobic
Saturated and unsaturated bonds

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Phospholipid Head

Polar (charged)
Hydrophillic

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Phospholipid bilayer’s permeability

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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How do molecules cross the cell membrane?

Simple diffusion

Facilitated diffusion

Primary active transport

Secondary active transport

Ion channels

Pink-/phago-cytosis

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Examples of simple diffusion

Blood gases, water
Urea, free fatty acids
Ketone bodies

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Facilitated diffusion examples

Glucose (hexose sugars)
GLUT family

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Primary active transport examples

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

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Secondary active transport examples

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

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Ion channels examples

Many sorts…
Voltage-gated
“Leak” channels

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Pino-/phago-cytosis

Vesicles

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Why are membranes and membrane proteins needed?

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

Tightly regulated
Disease disrupts this
Heart disease, kidney failure

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What is the membrane potential (Em)?

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

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Membrane potential

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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Convection of membrane potential dictates:

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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Nernst Equation

Slide 15

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Ion conductance (permeability) is key determinant of Em

Permeability is dependant on:

Channel numbers
Channel gating
Change ion permeability lead to change Em

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Kidneys and aldosterone:

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

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

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

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.)

Ischaemia

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?)

Epithelia

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

3 examples of epithelia

parietal cell (gastric pits)
intestinal epithelium
nephron

Substrate movement across membranes occurs with movement of water…

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

Epithelial cells in the nephron

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

How do cells communicate using cell membrane receptors?

Signal Transduction Internalise extra-cellular signal… First message into second message Many sorts

Types of receptors found in nucleus- nucleus steroid receptors

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

Signal transduction through ion channels

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

Signal transduction through membrane-bound steroid receptors

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

Signal transduction through neurotransmission

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

Signal transduction through growth factors

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

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

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

GPCR

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

+ve; makes cAMP:

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

-ve; prevents cAMP:,

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

+ve; makes IP3 and DAG:

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

How does pH effect membrane function?

Both extremes damage the protein Inhabits cell function

Critical role for acid-base homeostasis

Plasma Ca2+ Cell membrane excitability/permeability

Serum Calcium- 45% free ionised Ca2+

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

Serum calcium- 55% bound

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

How does temperature effect membrane function?

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

Regulation of the SAN action potential- hypothermia

Lowers depolarization rate of cardiac pacemaker cells Bradycardia (not vagally mediated) Abnormal heart rhythms Fibrillation (atrial and ventricle)

Hypovolaemia and the Lethal triad

Diagram slide 35

What is found in the phospholipid bilayer?

glycolipids: communication, joins cells to form tissues + stability glycoproteins: for cell to cell recognition + acts as receptors cholesterol: maintains fluidity in membrane

Occluding

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

Anchoring

ACTIN FILAMENTS INTERMEDIATE FILAMENTS HEMIDESMOSOMES

Actin filaments

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

Intermediate filaments

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.

Hemidesmosomes

anchor intermediate filaments in a cell to the basal lamina

Communicating gap junctions

allows the passage of small water-soluble ions and molecules