Membrane Ultra-Structure And Function Flashcards
Phospholipids are one of either:
Serine (phosphatidyl-serine)
Choline (phosphatidyl-choline)
Inositol (phosphatidyl-inositol)
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
Fatty acid tails
Non-polar
Hydrophobic
Saturated and unsaturated bonds
Phospholipid Head
Polar (charged)
Hydrophillic
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)
How do molecules cross the cell membrane?
Simple diffusion
Facilitated diffusion
Primary active transport
Secondary active transport
Ion channels
Pink-/phago-cytosis
Examples of simple diffusion
Blood gases, water
Urea, free fatty acids
Ketone bodies
Facilitated diffusion examples
Glucose (hexose sugars)
GLUT family
Primary active transport examples
Ions (Na+, K+, Ca2+, H+, HCO3-)
Water-soluble vitamins
Energy direct from ATP
Secondary active transport examples
Glucose (hexose sugars)
Symporters (Na+ + X)
Energy from ion gradient
Co-transport
Ion channels examples
Many sorts…
Voltage-gated
“Leak” channels
Pino-/phago-cytosis
Vesicles
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
What is the membrane potential (Em)?
Potential difference across the cell membrane generated by differential ion concentrations of key ions (K+, Na+, Ca2+, Cl-)
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
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
Nernst Equation
Slide 15
Ion conductance (permeability) is key determinant of Em
Permeability is dependant on:
Channel numbers
Channel gating
Change ion permeability lead to change Em
Kidneys and aldosterone:
Major role in K+ homeostasis
Renal failure
Conn’s Syndrome (too much aldosterone)
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
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
