ICPP (1-11) Flashcards
purpose of membrane
- control of the enclosed chemical environment
- communication
- recognition
- signal generation in response to stimuli- electrical or chemical
composition of the membrane (dry rate)
protein-60%
lipid- 40%
carbohydrates - 1-10%
membrane lipids
phospholipids, cholesterol and sphringolipids
phospholipids
predominant lipid
cholesterol
plasma membran elipid (45% of total lipid)
spingolipids
Spingomyelin
Glycolipids
Glycolipids
sugar containing lipid e.g. cerebrosides and ganfgliosides
Spingomyelin
only phospholipid not based on glycerol
membran lipids
amphiphatic
lipid bilayer formed by
forms when inc contact with an agues media- glycolipids can form either rebillers or micelles
- favour lipid bilayer
Bonds in the lipid membrane
Van der waals link hydrophobic tails
Hydrophilic heads linked by:
- Hydrogen bonds
- Electrostatic forces
Lipid dynamics
- flexion
- axial rotation
- lateral diffusion
- flip flop (rare– thermodynamically unfavourable)
protein dynamics
- lateral diffusion
- rotational
- conformational change
- NO FLIP FLOP- too thermodynamically unfavourable
single Nicholson model
mosaic lipid model
integral membrane proteins
e.g. channels
peripheral membrane proteins
do not run through the lipid bilayer- on the top
Erythrocyte membrane
- anatyis of the erythrocyte cell embark has revealed there are over 10 proteins making up the membrane
- Named 1-10
- Cytoskeleton is like a network of spectrum and actin
- spectrin winds together to form an antiparallel helix
- these are join by a short chain of actin, band 4.1 and ended with adducing molecules
- ankyrin (band 4.9) links spectrin and band 3 proteins
- Band 4.1 links spectrin and glycophorin A together.
- attachment to the integral proteins help restrict lateral movement of membrane proteins
Erythrocyte membrane malformation -
Haemolytic anaemia and hereditary ellipocytosis
Haemolytic anaemias e.g.
Hereditary spherocytosis- Spectrin
- levels are depleted up to 50%
- less robust cytoskeeltion
- rounded erythrocytes
- more prone to lysis and puts pressure on the spleen to remove due to decreased life space- haemolytic
Hereditary elliptocytosis
defect present in spectrin molecules leads defective formation of spectrin heterotramers 9rugby balls)
- leads to fragile ellipsoid erythrocytes
Membrane protein synthesis
1) AA,inp acid signal sequence a the N-terminus (hydrophobic)
2) signal sequence is noticed SRP
3) SRP halts protein synthesis
4) SRP caused ribosome and protein to bind to the receptor on the RER (docking protein)
5) signal sequence interacts with signal sequence receptor within proteins y
translocator cxomplex
6) Signal peptidase chops off the signal sequence
6) ribosome that is bound to complex translates peptide chain
secreted proteins
signal peptidase chops off signal sequence
membrane proteins
synthesis is arrested by stop transfer signal
- hydrophobic N terminus directed into the lumen and C terminal placed into the cytosol
Trasnport across membrane
passive
facilaited
active
passive
high conc to low conc
- no energy
facilitated
through channels e.g. through protein pores
through carriers (ping png)
gated channels (ligand, ion and gap junctions
Types of trransprters
uniport- one molecule in one driection
Symport- two molecules in one direction
Antiport- molecule in and out in opp direction
calcium in human body
> 1kg (99% in bones)
calcium is regulated by
by intestinal uptake, reabsorption in the kidneys and bone calcium regulation
calcium hoemsostias under
endocrine corntrol
- ca2+ in the parathyroid glands
- parathyroid hormeones
- 1,25 Dihydroxybita,ine D3
- calcitonin
calcium is much higher in
extracellular space
Why is calcium important
- muscle contraction
- neurotransmission
- fertilisation
- cell death
- regulation of metabolism
- learning and memory
Regulation of internal calcium (maintaining intracellular calcium)
- SERCA
- PMCA
- NCX
[calcium] intracellular
low
ATP dependent calcium homeostasis
PMCA (membrane)
SERCA (SR)
transporters of calcium out of the cell
NCX- sodium calcium exchanger
- antiport
cell membrane is relatively impermeable to
calcium
mechanisms that increase intracellular calcium
- voltage gated calcium channels (VOCCs)
- ligand gated ion channels (LGIC)
calcium movement out of the ER/SR
Found on the ER/SR membrane:
1) Calcium induced calcium release- Ryanodine receptors
2) IP3R
pH regulation occurs based on the amount of
protons and hCO3- in the cells
- controlled by ion channels
Acid extrusion
when H+ is expelled form he cell, increasing pH
alkalisation is
opposed by expulsion of HCIO3-
water does not
have a concentration
cell shrinkage
ions will move in (same amount of positive and negative ions) e.g. Na+ and Cl-
- water will move in
cell swelling
ions will move out
- water will follow
measuring membrane potentials
uses micro electrode- which is a fine glass pipette
- filled with conducting solution (KCL)
-
resting membrane potnetial
electrical change that exist across a membrane
- always expressed as the potential inside the cell relative to the extracellular solution
- mV
Cardiac myocytes
-80mV
Neurones
-70
smooth muscle
-50
skeletal muscle
-90
equilibrium potentials of calcium
Eca +122mV
equilibrium potentials of sodium
+70mv
equilibrium potentials of K+
-95mV
equilibrium potentials of Cl-
-96mv
nicotinic ACh receptor found at the
NMJ
- ACH binds, which causes the sodium and potassium to flow through
- causing AP to be propagated across a neurone
types of gated channel
ligand gated
voltage gated
mechanical gated
Action potential is a
change in voltage across the membrane
action potential depend on
ionic gradients and relative permebaility
AP will only occur
if threshold is reach - all or nothing
- can propagate across without loss of amplitude
AP
- influx of sodium ion (moves towards sodium equilibrium (70mV) (positive feedback)
refractory periods
1) Absolute refractory period
2) Relative refractory period
Absolute
time between intitial opening and closing of the sodium channels
- NO ACTION POTNETIAL can be generated
relative
time it takes for inactive sodium channels to recover
- if there is a strong enough stimulus it will genrate an AP
local anaesthetics
act by binding to and blocking sodium channels- preventing generation of an AP
anaesthetics are
weak bases
Anaesthetics block conduction in nerves ions he following order
- small myelinated axons
- unmyelinated axons
- large myelinated axons
conduction velocity of AP
distance/time
a change in membrane potential in one part can strand to the
adjacent areas of threw axon.
conduction velocity affected by
affected by:
- high membrane resistance e(less ions channels opne- less current open)
- capacitance- ability to charge
- large axon diameter
myelinated areas created
saltatory conduction
- ## conduction jumps from nodes of ranvier
which cells form myelinated axons
- Schwann
- Oligodendrites
demyelination e.g.
Multiple sclerosis
- muscle weakensss
- visual problems
- fatigue
when AP gets to the end of the nerve
NT release in cleft between NMJ
what causes NT release
AP opens calcium channels and calcium causes vesicle to fuse with pore- exocytosis
NMJ
1) ACH released
2) binds to receptor on the sarcolemma
3) sodium influx
4) depolarisation
5) conduction down T-tubule
6) stimulates ryanodine receptor- calcium relase
7) calcium bins to TnC subunit of tropinina nd contraction cycle begins
blockers of ACH receptors
- competitive blockers
- depolarising blockers
myasthenia gtavis
antibody targets ACh receptors on p[sot synaptic membrane
- muscle weakness
myasthenia graves
antibody targets ACh receptors on p[sot synaptic membrane
- muscle weakness
signalling targets
RITE
RITE
R receptors
I ions channels
T transporters
E enzymes
Types of receptors
KING
KING
K- kinase linked receptors
I -ion channels
N- nuclear intracellular
G- G protein couple receptors
alpha S
stimulate
alpha I
Inhibits
QISS
QIQ
Q- A1
I- A2
S- B1
S - B2
Q- M1
I- M2
QM3
GPCR
7 transmembrane
- transduce signals generated by agonsits
GPCR sturcuture
heterotirmeric- 3 subunits
stops involved with GPCR
1) agonist bidnigns
2) stimulates GDP tp GTP exhange and dissociation nd aloha beta gamma subunuts
3) subunits go onto have different affects
alpha S subunits
activates AC
- hydrolyses ATP to cAMP
- cAMP os secondary messenger which activates PKA
- PKA phosphorylates to increase/ decrease other proteins activity
e.g. of alpha S subunit agonist
peptides
glucagon
insulin
alpha Q subiunit
1) agonist bins
2) GDP for GTP exchange
3) Alpha Q stimulates phospholipase C
4) hydrolysis of PIP2 –> IP3 and DAG
5) DAG stimulates PKC
6) IP3 binds to receptor on SR- calcium release
signal amplificaiton
one GPCR that a citrated causes sequential GTP/GDP exchange
- activate molecules released that a citrate several other effector molecules
- effector molecules binds to many other proteins
regulation of chronotropy (rate of heart)
ACH binding to M2
- Alpha I
- -> inhibition of AC
- -> opens more potassium channels
- -> Slows down rate of firing (reduced chronotropy)
regulation of inotropy
Sympathetic innervation
- ligand binding to B1 receptors
- Alpha S unit
- increase in cAMOP- VOCC channels
- positive isotropy effect
