Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ESA two revision > M and R > Flashcards

M and R Flashcards

1
Q

What are the general functions of membranes?

A 
Selective permeable barrier
enclosed environment
Communication
recognition of signaling molecules
signal generation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some of the specific functions a membrane can have ?

A 
Interaction with adjacent cells
absorption or secretion
changing shape for transport
synapses
electrical signal conduction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the composition of a plasma membrane

A

40% lipid
60% Protein
1-10% carbohydrates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How are plasma membranes stabilised?

A

H bonds with h2o

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Give an example of a phospholipid

A

Phosphatidylcholine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Give an important property of phospholipid molecules

A

Amphipathic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are phospholipid molecules named?

A

By their head

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How can chain length of phospholipid molecules vary ? What are the most common lengths?

A

C14-C24

Most common C16 and C18

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the structure of a phospholipid

A

Glycerol backbone, 2 FAs with phosphate group and head

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is a plasmalogen? Give an example of one

A

Lipid not based on glycerol eg sphingomyelin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a glycolipid?

A

Lipid containing sugar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the two types of glycolipids?

A

Cerebroside - contain a sugar monomer

Ganglioside- contain a sugar oligosaccharide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What movements are lipid able to do in a bilayer?

A

Flip flop
Rotation
Lateral drift
Flexion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

A double bond in a phospholipid has what effect?

A

Introduces a kink reducing packaging and therefore increasing fluidity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How can a protein move in a bilayer?

A

Rotation. lateral drift and conformational change

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What type of movement can a lipid do but not a protein in a plasma membrane?

A

Flip flop - requires too much energy for the hydrophobic and hydrophilic moieties to swap.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe an integral protein

A

Hydrophobic interactions with membrane - has at least one transmembrane domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe a peripheral protein

A

Held in place by electrostatic interactions or H bonds - no transmembrane domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What evidence is there for proteins ?

A

Freeze fracture
Fractionalization and SDS page
Specificity of function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why do proteins have reduced movement than lipids?

A

Tethering to cytoskeleton
Aggregates
Lipid mediated effects - areas of low cholesterol
Basolateral junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where would you find the cytoskeleton?

A

Cytostolic face of membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe spherocytosis anemia

A

Spectrin depleted by 40-50% leading to spherical shaped RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe eliptocytosis

A

Defect in spectrin meaning they are unable to form tetrameres leading to fragile ellipoid cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is topology?

A

Mechanisim of inserting proteins meaning proteins have very specific orientation in the membrane- membranes are therefore asymmterical.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What proportion of a membrane is cholesterol?

A

45%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How does cholesterol stabilise the membrane ?

A

Through H bonds
CHOLESTEROL ABOLISHES THE ENDOTHERMIC PHASE TRANSITION OF THE LIPID BILAYER
The sterol ring decreases packaging and increased fluidity
The long tail reduces chain motion decreasing fluidity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What types of molecules are able to easily pass through the bilayer?

A

Hydrophobic - oxygen, carbon dioxide, nitrogen and benzene

Small uncharged polar molecules - water, urea, and glycerol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What molecule cannot pass through the bilayer?

A

Ions

Large uncharged polar molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the uses of proteins in the bilayer?

A

Maintain ionic composition
Maintain cell volume
Maintain pH
Concentration of metabolites and anabolites
Remove waste products
Generation of ionic gradients for function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What does diffusion depend on?

A

Gradient and permeability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What three methods of transport are there when using a protein?

A

Uniport
Antiport
Symport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the problem with transport of molecules using proteins ?

A

They are saturatable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Give the extracellular concentration of Na ions

A

145mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Give the extracellular concentration of Cl ions

A

123mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Give the extracellular concentration of Ca ions

A

1.5mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Give the extracellular concentration of K ions

A

4mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Give the intracellular concentration of Na ions

A

12mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Give the intracellular concentration of Cl ions

A

4.2mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Give the intracellular concentration of Ca ions

A

10-7M

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Give the intracellular concentration of K ions

A

155mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Describe and give the properties of the Na+ pump

A

3 sodium out
2 K in
Uses one ATP
Provides the concentration gradient and therefore energy for lots of secondary active transports

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Describe the NCX transporter

A

sodium calcium exchanger
1 calcium out for 3 sodium in
Low affinity high capacity
Electrogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Describe the PMCA

A

Plasma membrane Ca ATPase
One calcium out for one H in
Brings in H to increase electrochemical efficiency
High affinity low capacity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Describe the SERCA

A

Sarco(endo)plasmic reticulum Ca ATPase
One calcium out for one H in
located on ER - creates store of Ca

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Describe the NHE

A

one H out for One sodium in

extrudes acid using NA gradient - role in pH conc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Describe the AE

A

Anion exchanger
Bicarbonate out and Cl in
Extrudes base and electrochemically neutral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How do proteins help control cell volume?

A

Movement of osmotically active ions or organic osmolytes - h20 follows

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

How do proteins help control cell pH?

A

Using Na gradient

Extrude / influx acid or base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the membrane potential ?

A

Electrical potential different across a membrane controlled by movement of ions
-20–90mV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the equilibrium potential ?

A

The potential difference across a membrane that is selectively permeable to only that ion- electrical chemical gradient equals concentration gradient leading to no net movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How do you calculate the equilibrium potential for an ion?

A

Use of the Nernst Equation

E= 61/Z log 10 (conc out/ conc in)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

How is the resting membrane potential brought about?

A

Membrane selectively permeable to K+
K+ down concentration gradient and in down chemical gradient but anions cannot follow making cell negative compared to outside.
Na pump has minor role but is mainly used to created gradients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What types of gating are there?

A

Ligand - Fast ( intrinsic ion channel) slow ( GPCR)
Mechanical
Voltage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Give four properties of an AP

A

All or nothing
Only occur if reach threshold
Distinct signals
Propagated without loss of amplitude

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Define depolarisation

A

Cell interior less negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Define hyperpolarisation

A

Cell interior more negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

During the AP which ions conductance changes rapidly and which one slowly

A

Na - quickly

K- Slowly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What type of feedback is involved in an AP?

A

Postive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Describe the channel and ion channels leading to depolarization and then repolarisation?

A

Na channels open leading to Na entering the cell which increases the number of Na channels open and therefore the influx of Na into the cell. This depolarises the cell.
Depolarisation opens K channels leading to influx of K into the cell and causes inactivation of Na channels stopping the Na influx resulting in repolarisation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What happens during the absolute refractory period ?

A

All Na channels are inactivated- excitatory of cell is at 0

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What happens during the relative refractory period?

A

Na channels are recovering- excitability returns to normal as number inactivated decreases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Describe accommodation

A

Constant sub threshold stimulus leads to more and more Na channels in the inactivated state meaning a larger stimulus for AP to be generated.
Eventually AP cannot be generated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Describe the structure of a Na channel ?

A

1 subunit = 4 domains = 1 functional protein

6 transmembrane domains - S4 channel voltage sensor- stimulated by change in transmembrane voltage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Describe the structure of a K channel?

A

1 subunit = 1 domain = 1/4 functional protein

Need 4 subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is the length constant?

A

Distance it takes for initial signal to fall by 37% of original amplitude

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What affects the length constant?

A

Diameter - larger = faster
Resistance - higher = faster
Capacitance - lower = faster

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What is the effect on transmission of myelination? Why?

A

Quicker at larger axon diameter due to saltatory conductance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What effect does myelination have on resistance and capacitance ?

A

Increased resistance

Decreased capacitance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Where is high density of ion channels found in a myelinated neurone?

A

At nodes of ranvier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Describe the consequences of MS

A

Demyelination of neurones leads to a decreased length constant
Initially - total blockage of signal
Later - slower conductance as channels spread along the axon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

How do you calculate unmyelinated neurone speed?

A

Proportional to square root of diameter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What is the maximal speed of an unmyelinated neurone?

A

20ms-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

How do you calculate the speed of a myelinated neurone?

A

Proportional to diameter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What is the maximal speed of an myelinated neurone?

A

120ms-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

At what point does speed in myelinated neurone equal that of unmyelinated?

A

1mm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Describe neurotransmitter release?

A

Ca entry though Ca channels bind to synaptotagmin
Vesicles brought close to membrane
Snare complex make a fusion pore
Transmitter released through this pore

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What heads can you find on a phospholipid? What property do they all have ?

A

Choline, amine, amino acid, sugar

All polar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Describe the formation of the bilayer?

A

Amphipathic molecules form bilayer spontaneously in h20 driven by VdWs between hydrophobic tails
Structure is then stabilised by non covalent forces ; electrostatic and H bonds between hydrophilic moeites and interactions between hydrophillic moeites and h20

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

How are peripheral protiens removed?

A

pH or ionic strength

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

How are integral proteins removed?

A

Agents that compete for non polar interactions with bilayer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

How is the orientation of proteins in the membrane determined?

A

Protein synthesis determines this with addition of highly hydrophobic stop transfer sequence. When protein is being translated and fed into ER lumen. The stop signal will remain in the ER once it has been translated - rest of the protein is translated in cytoplasm and protein will then span the membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Give the properties of the stop transfer sequence

A

18-20 AA

Hydrophobic smaller uncharged AAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What is a hydropathy plot? What are the axis?

A

y= hydropathy index
x= aa number
Shows how hydrophobic/ hydrophilic an AA sequence is
Can work out the number of TMDs a protein has

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Define facilitated diffusion

A

Permeability of membrane to a substance is determined by specific proteins in the bilayer - modes include carrier molecules and channel proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What substance inhibits the Na pump?

A

Oubain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What happens to the NCX in ischaemia?

A

Decreased ATP so no Na pump leading to an increase in Na conc in the cell so the NCX reverses drawing Ca into cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What control is there on the NHE?

A

Activated by growth factors and inhibited by amiloride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Describe bicarbonate reabsorption in the proximal tube?

A

Na pump removes Na- NHE can therefore pump Na from the lumen into cells along gradient in exchange for H ions - H into lumen and picks up HCO3- bringing into cell.
Used to retain base for buffers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What are aquaporins?

A

Allow h2o to move increased easily through membrane - inclusion in membrane in kidney epithelial cells stimulated by ADH increasing water reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Describe loop diuretics ?

A

Block Na uptake in thick ascending limb of loop of henle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Describe amiloride

A

Potassium sparing diuretic acts on both ENAC and proximal NHE tubules to prevent Na reuptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Describe the effects of excess aldosterone

A

Up regulate ENAC and NHE to increase Na uptake - contribute to hypertension
Treated by spironolactone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Describe glucose uptake

A

SGLUT1 - Na and glucose mover through faciliated diffusion- using conc gradient from Na pump
GLUT transport moves glucose from cell to blood stream
GLUT 1&3 found throughout the body - maintains basal level
GLUT 2 found in hepatocytes and pancreatic b cells
GLUT 4 found in striated muscle and adipose cells - insulin stimulates up regulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

How is it maintained that glucose never moves back into the lumen of the vessels from cells ?

A

Glucose is quickly converted into glucose-6-phosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

What type of molecules move via passive transport?

A

Non polar molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

How does rate change with changing the concentration gradient in passive transport?

A

Rate increases linearly with increase conc gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Describe the difference between active transport and other types of transport

A

Requires energy from ATP hydrolysis/ electron transport/ light
Against unfavorable conc and or electrical gradient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Describe the mitachondrial uniporter

A

High conc to buffer when potientally harmful- one ca in for breakdown of one ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Explain the issue with transporters in cystic fibrosis

A

Transport of Na of cell by Na pump allows NKCC2 channel but faulty CFTR protein leads to accumulation of Cl- in cell meaning water moves into cell via osmosis and viscous mucus in lumen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Explain the issue with transporters in diarrhoea

A

CFTR over activated by phosphorylation PKA- Cl- excessively transported into lumen water then follows.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

In a 70kg male how much water is there? What is the breakdown of this ?

A

42L
Intracellular 28L
Extracellular 14L - interstitial 9.4L, plasma 4.6L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What would happen if there was a sudden change in Na levels ?

A

increase would lead to peripheral oedema or decrease would lead to shrinkage of interstitial space and blood volume –> organ misfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

How is resting membrane potiental expressed?

A

Potiental inside the cell relative to outside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

How can you measure a membrane potential ?

A

Using a very fine micropipette that can penetrate the cell and is filled with conducting solution KCl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

What is the resting membrane potential of nerve cells?

A

-50–75mV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

What is the resting membrane potential of smooth muscle cells?

A

-50mV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

What is the resting membrane potential of skeletal / cardiac muscle ?

A

-80–90mV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Why is the resting membrane potential not equal to Ek of potassium?

A

Other ion channels are open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

What does changing the permeability of K have on the membrane?

A

Changes Ek therefore changes resting potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

What ions cause depolarisation of a membrane ?

A

Na and Ca

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

What ions cause hyperpolarisation of a membrane?

A

Cl and K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Describe fast synaptic transmission

A

Receptor is also an ion channel
Depolarising transmitter open channels with a positive reversal potential leading to excitation in cells causing excitatory post synaptic potential
Hyperpolarising transmitter open channels with -ve reversal potentials leading to an inhibitory post synaptic potential.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Describe slow synaptic transmission

A

Signal leads to channel being opened via a GTP binding protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

Define an action potential

A

Change in voltage across a membrane. they are dependent on ionic gradient and relative permeability of the membrane. Generated by an increased permeability to Na in the membrane leading to movement towards Ena

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

What happens to other channels during an action potential?

A

open or close brought on by a conformational change

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Why does the cell go into a state of hyperpolarisation after depolarisation in an AP?

A

Voltage gated k channels open therefore increased conductance of K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Describe the actions of procaine and its usage

A

Topical anaesthetic for medicine and dental surgery- vasoconstrictor and increases quality of anaesthetic.
Binds and blocks Na channels meaning AP cannot rise
Blocks conduction small myelinated axon, non myelinated axon and large myelinated axon so SENSORY BEFORE MOTOR
2 pathways
hydrophobic - pass through membrane becoming charged
hydrophilic- use dependent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Describe propagation of an action potential

A

Change in membrane potential at one part of the membrane affects adjacent sections of axon
local current causes spread of current
conduction velocity determined by how far axon current can spread
AP initiated at site of depolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

How does high membrane resistance lead to high conduction velocity?

A

Number of channels open - lower resistance increased channels open and more loss of local current across membrane limiting spread of current

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

How does low membrane capacitance lead to high conduction velocity?

A

Capacitance is the ability to store charge - high capacitance more current to charge and cause a decrease in spread of local current

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

Why does large axon diameter lead to high conduction velocity?

A

Decreased cytoplasmic resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

Describe the composition of myelin

A

40% h2o
Dry mass
70-85% lipid and 15-30% protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

Which neurones is it easier to stimulate using electrodes and why?

A

Myelinated neurones as decreased capacitance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

When does myelination start during development and when does it finish?

A

4th month of development and continues into 1st year of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

How long does regeneration in PNS take ?

A

1-3mm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

Where are L type calcuim channels found?

A

Lungs, muscle and neurones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

What chemical blocks L type calcuim channels?

A

Dihydropyridines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

What types of calcuim channels are found in the heart?

A

R and T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Describe the structure of calcium channels ?

A

Very simillar to Na channels

Extra proteins enabling correct regulation including glycosylation and phosphorylation sites

130
Q

What are the blockers of nACHr?

A

Competitive and non competitive

131
Q

Describe and give an example of a competitive blocker on nACHr?

A

Tubocurarine
Fits where ACH does - over come by increasing Ach conc
same amount of Ach will cause less depolarisation so may not reach threshold

132
Q

Describe and give an example of a non competitive blocker on nACHr?

A

DEPOLARISING BLOCKER eg succinycholine
maintains depolarisation inhibits Achesterase
Na channels are inactivated and receptors desensitised.
sodium channels cannot activate adjacent ion channels as they are inactivated leading to MEPP - mini end plate potentials being activated.

133
Q

What are MEPP?

A

mini end plate potentials - small random spontaneous release of vesicles causing a small amount of neurotransmitter being released

134
Q

Describe myasthenia gravis and the treatment

A

nAchR receptors activated by target antibodies causing weakness and a reduction in end plate potentials amplitude
Treat with AchEsterase

135
Q

What is ca needed for?

A

Control of fertilisation, proliferation, secretion, neurotransmitter, metabolism, contraction, memory , apoptosis and necrosis.

136
Q

What are the advantages and disadvantages of maintaining the large gradient between Ca conc in and outside a cell?

A

Advantage - changes in conc occur rapidly with little Ca movement
Disadvantage - ca leads to loss of regulation and death

137
Q

How is the large gradient in Ca set up?

A

Relative impermeability of the plasma membrane
Ability to expel Ca across the membrane
Ca buffers
Intracellular stores ( rapidly releasable and not)

138
Q

Explain the activation of CaATPase?

A

Increased Ca conc
Ca binds to calmodulin
Ca- calmodulin complex binds to ATPase and ATPase removes Ca

139
Q

What effect does buffers have on the ability of ca to diffuse?

A

Decrease as diffusion dependent on conc of binding molecule and level of sat

140
Q

How is release from intracellular storage of calcium mediated?

A

By GPCRs activating Gaq which binds to phospholipid PIP2 releasing IP3 which binds to SERCA triggering release
CICR- Ca binds to ryanodine receptors on side of S/ER triggering release of increased Ca

141
Q

In what organ is CICR very important and why?

A

Cardiac myocytes for coordinated powerful contraction- early depolarisation also allows NCX to reverse leading to increased Ca into the cell

142
Q

Where is the non rapidly releasable store of Ca in the cell?

A

Mitachondria

143
Q

When does uptake into non rapidly releasable ca stores occur?

A

When Ca conc high and in normal conditions to create microdomains

144
Q

What is the function of Ca uptake to the mitachondria?

A

Ca buffering
regulate pattern and extent of signalling
stimulation of mitachondrial metabolism ( increased Ca increased Met increased ATP )
Role in apoptopic cell death

145
Q

Describe ca store refilling

A

Termination of signal
Ca is recycled using store operated channels based on depleted signal - specific proteins interact following depletion to activate channels (STIM and ORAI)

146
Q

What chemicals may be used during chemical signals?

A

Hormones, neurotransmitters and local chemical mediators

147
Q

Define a ligand

A

Any small molecule that binds specifically to a receptor site

148
Q

define a agonist

A

a ligand that produces activation of a receptor

149
Q

define an antagonist

A

a ligand that combines with a receptor site without causing activation

150
Q

define a partial agonist

A

agonist that stimulates a receptor but are unable to elicit maximal cell response

151
Q

define a receptor

A

a molecule that specifically recognises a ligand or family of ligands and in response to binding brings about regulation of a cellular process.
UNBOUND THEY ARE FUNCTIONALLY SILENT

152
Q

define an acceptor

A

operate in absence of a ligand - binding of a ligand has little or no effect

153
Q

How can signaling between cells be done?

A

Secreted molecules or siganlling via plasma membrane bound molecules using adhesion molecules

154
Q

Define paracrine

A

local chemical mediator secreted into interstitial space and bind with adjacent cells causing a whole tissue response

155
Q

Define endocrine

A

hormone released into blood stream and arrives at distal site to cause a response

156
Q

Where are hydrophilic molecules receptors?

A

On the cell surface

157
Q

Where are hydrophobic molecules receptors ?

A

Intracellular - nucleus or cytoplasm

158
Q

Give some simillarities between receptors and enzymes

A

specific sites
binding governed by shape of binding cleft
binding is reversible
specificity of binding confers specificity to regulation of process involved
binding induces a conformational change and change is activity of molecule
no chemical modification of ligand in binding

159
Q

Give the differences between receptors and enzymes

A

Affinity - receptors higher affinity
ligand binded to receptor site is not modified chemically whereas substrate bound in an enzyme if modified in chemical reaction catalysed by active site

160
Q

How are receptors classified?

A

Specific physiological signalling molecule recognised

Affinity to a series of antagonists

161
Q

Explain the process of signal transduction by membrane bound ion channel

A

Membrane bound ion channels- binding leads to conformational change and opening of gated ion channels permitting flow of ions eg nAchR, GABA, gylcine and glutamate

162
Q

Describe the structure of a membrane bound ion channel

A

Classic -Pentameric structure - 4 TMDs- 1 lining pore, 2 bind ligand and each has charge attracting ions
SEE DIAGRAM
Non classic - eg IP3

163
Q

Explain the process of signal transduction by membrane bound receptor with integral enzyme activity

A

Ligand binds to extra cellular domain of receptor activity causing conformational change activating intrinsic enzyme activity contained within the structure of the receptor
eg growthe factor receptors for insulin, EGF and PDGF linked to tyrosine

164
Q

Explain tyrosine kinase linked receptors

A

Binding of hormone to binding sites activates protein kinase activity in cytoplasmic domain which autophosphorylates tyrosine residues on cytoplasmic domain of receptor. This is recognized by transducing proteins or directly by enzymes containing phosphotyrosine recognition sites. The enzyme is then activated by phosphorylation or allosterically.

165
Q

Explain the process of transduction via membrane bound receptors which couple to effectors via GTP binding regulatory proteins to enzymes or channels

A

Receptor bindinf results in a conformational change which activates a GTP/GDP exchange in GTP binging regulatory proteins
eg mAchR and all adreonceptors

166
Q

Describe the structure of a GPCR

A

7 TMDs
N cytoplasmic C in cell part of G protien coupling domain
LOOK AT SHEET

167
Q

Describes signal transduction via intracelllular receptors

A

Binds to monomeric receptors in cytoplasm or nucleus
Stabilized in resting state by HSP or chaperone proteins - activated receptor dissociates from chaperone protein in nucleus where it binds to control regions in DNA defined by specific sequences leading to regulation of gene expression

168
Q

Describe by the structure of intracellular receptors

A

C region- binding domain
Middle - DNA binding domain
N region - nothing

169
Q

How is amplification achieved?

A

Cascade

170
Q

What in lay mans terms is receptor mediated endocytosis?

A

Membrane internalisation

171
Q

What cells can perform phagocytosis?

A

neutrophils and macrophages

172
Q

Explain the process of phagocytosis?

A

Particles bind to receptor in plasma membrane, cell extends pseudopod to permit further interactions and membrane evagination and particle internalisation via membrane zippering mechanism.
Internalised phagosome then fuses with a lysosome forming a phagolysosome and particle is degenerated

173
Q

Define pinocytosis

A

invagination of plasma membrane to form lipid vesicle permits uptake of impermeable extracellular solutes and retrieval of PM.

174
Q

What are the two types of pinocyosis

A

Fluid form and receptor mediated endocytosis

175
Q

Define receptor mediated endocytosis

A

Selective internalisation of molecules into cell by binding of molecules to specific cell surface receptor

176
Q

Describe the uptake of cholesterol by receptor mediated endocytosis

A

LDLs bind to receptors for ApoB on clathrin pits which form spontaneously these are invaginated and pinch of the PM to form coated vesicles. The vesicles are uncoated by an ATP dependent process and then fuse with larger smoother vesicle endosome. In the endosome the receptor and LDL dissociate. The transmembrane receptors is sequestered off to a domain within endosome membrane budding off as a vesicle to be recycled. LDL is then degraded

177
Q

Describe an LDL particle

A

Originates in the liver
core of cholesterol molecules esterified to FAs surrounded by a lipid monolayer containing phospholipids cholesterol and ApoB.

178
Q

Which cells express an ApoB receptor

A

Those requiring cholesterol

179
Q

Why does the receptor and ligand dissociate in the endosome?

A

Endosome ph 5.5-6 maintained via ATP dependent proton pump

180
Q

Describe the structure of of clathrin coated pit

A

Minimum stucture - triskeleton ( 3 legged) contain clathrin and 2 light chains
Triskeletons associate to form basket structure making hexagon and pentagon structures

181
Q

Describe the uncoating of a clathrin pit

A

Carried out by an ATP dependent uncoating protein which binds and stabilises the freed coated proteins

182
Q

How is the clathrin pit attached to the PM and what is its function?

A

By a number of integral membrane adapter proteins which form associations both with clathrin and receptors.
Locate receptors over the clathrin pit

183
Q

Describe the defects that may be present in the receptors in a patient with hypercholesterolaemia?

A

Receptor deficiency- prevent expression of LDL receptor
Non functional receptor
Receptor binding normal - no internalisation due to deletion of C terminus meaning no interaction with a clathrin pit

184
Q

Describe iron uptake

A

2 Fe3+ ions bind to apotransferrin forming transferrin which binds to receptors at neutral pH and is internalised. At acidic pH iron is released by apotransferrin remains bound to the receptor- complex is sorted in CURL for recycling back to PM.
Ligand and receptor are recycled

185
Q

Describe uptake of occupied insulin receptors

A

Only over clathrin pits when bound as binding induces a conformational change so now recognised by clathrin pits. In CURL insulin remains bound to receptor and complex is degraded by lysosome
Ligand and receptor are both degraded

186
Q

Why is it beneficial that both the ligand and the receptor are degraded in insulin receptor uptake ?

A

Allows for the reduction in number of insulin receptors on membrane desensitising the cell to continues high levels

187
Q

Explain the process of transcytosis

A

Ligands remain bound to receptors and are transported accross the cell

188
Q

Give and explain an example of transcytosis

A

Maternal immunoglobulins to foetus via placenta
Transfer of immunoglobulin A from circulation to bile to liver - during this receptor cleaved resulting in release of immunoglobulin with bound secretory component from receptor

189
Q

What two pathogens take advantage of receptor mediated endocytosis?

A

Chlorea and diptheria

190
Q

How do pathogens take advantage of receptor mediated endocytosis?

A

Binding to cells by fotuitous association with cell receptors and entering cells via pits - unfolding hydrophobic domains in membrane fusion proteins at lower pH. They they insert the membrane fusion proteins into endosome membrane leading to this fusing with the membrane and release of the genomic RNA into cell cytoplasm. They then use the host machinery to replicate RNA and caspid proteins to bind new viruses at cell membrane.

191
Q

Why must signal transduction occur?

A

Most signals cannot enter cells to cause a response so must activate a protein on the cell surface and use this to transduce into the cell.

192
Q

How do G proteins alter activity of effectors?

A

Via activation of guanine nucleotide binding proteins

193
Q

What are G proteins responsible for?

A

Muscle contraction, stimulus secretion coupling, catabolic and metabolic processes , light/smell and taste perception

194
Q

Describe the structure of G proteins

A

Same generic heteromeric structure made up of 3 subunits ( alpha, beta and gamma)
Beta and gamma bind each other so tightly they can be classed as one unit

195
Q

Describe the method of activation and termination of activation of G proteins

A

1) Basal state G protiein present at inner face of PM predominately in heteromeric form
2) Alpha subunit binds guanine nucleotide of GTP to hydrolyse to GDP
3) Activated receptor has high affinty for G protein and protein -protein interactions.
GDP released from alpha subunit and replaced by GTP
4) Binding of GTP reduced affinity of aplha subunit for receptor and beta-gamma subunit. Therefore these are released to interact with effectors
5) Effector interactions is terminated by intrinsic GTPase activity of alpha subunit turning GTP back to GDP leading to increased affinity again.

196
Q

Why can a G protein be classed as an on off switch?

A

On - receptor facilitated GTP/GDP exchange

Off- determined by time taken for GTP hydrolysis ( timer function)

197
Q

How does cholera interact with a G protein?

A

Deactivation of Gs protein mediated signalling inrreversibly- Gsa subunit uncouples

198
Q

How does pertussis interact with a G protein?

A

Prevents Gi protein activation by GPCRs- irreversibly

199
Q

What does cholera and pertussis interaction with G proteins have incommon?

A

ADP- ribosylate specific G proteins

200
Q

What are the signalling cascade three components ?

A

Receptor
GPCRs
Effector molecule (ion channel or enzyme )

201
Q

What is the consequence of activation of Gs ?

A

Increased adenylyl cyclase leading to lipolysis and glycogenolysis

202
Q

What is the consequence of activation of Gq ?

A

Increased phospholipase C leading to Smooth muscle contraction

203
Q

What is the consequence of activation of Gi?

A

Decreased levels of adenylyl cyclase and stimulation of k channels leading to slowing of cardiac pacemaker

204
Q

What is the consequence of activation of Gt?

A

Stimulation of cyclic GMP phosphodiesterase leading to visual excitiation

205
Q

What does cyclic GMP phosphodiesterase do ?

A

hydrolyses cyclic GMP to 5’ GMP

206
Q

What does phospholipase C do?

A

PIP3 –> InsP3 and DAG

207
Q

Mutations to GPCRS cause what?

A

disease through loss or gain of function

208
Q

What is retinitis pigmentosa?

A

Loss of function mutation to rhodpsin

209
Q

What is nephrogenic diabetes insipidus?

A

Loss of function to V2 vasopressin receptors

210
Q

What is familial male precocous puberty?

A

Gain of function mutation to LH receptor

211
Q

What is the function of adenylyl cyclase ?

A

Hydrolyses cellular ATP to generate cyclic AMP which interacts with specific protien kinases to phosphorylate a variety of other proteins within a cell

212
Q

What is the effect of increased adenylyl cyclase?

A

Glycogenolysis, gluconeogenesis, lipolysis

Relaxation of variety of types of smooth muscle, positive inotrophy and chronotrophy

213
Q

What is the function of phospholipase C?

A

Membrane phospholipid PIP to IP3 which interacts with specific intracellular receptor on ER to allow Ca ions into cytoplasm

214
Q

Describe the deactivation pathways of GPCRs?

A

While activated receptor susceptible to variety of kinases that phosphorylate the receptor and prevent it activating further G proteins - desensitisation phenomenon
Lifetime of alpha GTP may be limited by cellular factors that interact GTPase
Basal states are favoured
Enzymatic cascades activated downstream - act to oppse GPCRs effect

215
Q

Explain the regulation of chonotrophy of the heart?

A

Rate of AP generation can be affected by Ach release to M2 receptors which increase potassium channel opening leading to hyperpolarisation slowing intrinsic firing rate resulting in negative chronotropic effect.

216
Q

Explain the regualtion of inotrophy of the heart?

A

Circulating adrenaline and sympathetic innervation B1 receptors activated causes increase open probability of voltage operated calcuim channels.
Gs also indirect effect by increasing cAMP –> PKA –> phosphorylation and activation of VOCC leading to influx of Ca

217
Q

Explain the regulation of arteriolar vasoconstriction

A

NA on alpha 1 receptors to stimulate phospholipase C and IP3 production via Gq- IP3 release on ER ca leading to contractile response

218
Q

Explain the regulation of modulation of neurotransmitter release?

A

Presynaptic GPCRs can influence the release eg pre synaptic u-opoid receptors stimulated by endogenous opoids or analgesics to couple Ga1
Gby subunits liberated interact with VOCC to decrease Ca release

219
Q

Where do drugs bind to ?

A

Receptors or proteins - GPCRs and enzymes most common

220
Q

What concentration is important in determining drug action?

A

Concentration of drug molecule around receptor

221
Q

When do drugs have the same concentration of drug molecules?

A

Drugs with equivalent molar conc NOT equivalent conc by weight

222
Q

How many particles does 1M contain?

A

6x10^23

223
Q

What is drug receptor binding governed by?

A

Association and dissociation rates - related to concentration of reactants and products

224
Q

What must a substance have to be an agonist?

A

Both affinity and efficacy

225
Q

What does an antagonist have in terms of affinity and efficacy?

A

ONLY affinity

226
Q

What is affinity?

A

Likelihood of ligand binding to its target.

Reciprocally measured by dissociation constant

227
Q

What is efficacy?

A

Likelihood of activity - governs receptor activation

228
Q

What is Bmax?

A

Max binding capacity- information about receptor number

229
Q

What is Kd?

A

Dissociation constant ( measure of affinity)- conc needed for 50% occupancy

230
Q

What does a small Kd show?

A

Increased affinity

231
Q

What is Kd known as if it is determined pharmalogically?

A

Ka

232
Q

What does a conc response curve show?

A

Response in cells/ tissue

233
Q

What does dose response curve show?

A

Response in whole body

234
Q

What is E50?

A

Effective [ ] giving 50% maximal response - measure of potency

235
Q

What is potency?

A

Combination of affinty, efficacy and number of receptors - tissue dependent factors
How good a drug is at generating response measured by EC50.

236
Q

What is I50?

A

Inhibitory drugs - inhibitory concentration gicing 50% of maximum inhibition

237
Q

With the same Emax does a drug have to have the same efficacy?

A

No could have different affinity

238
Q

What is asthma?

A

Reversible airflow obstruction and bronchiospasm

239
Q

What is the treatment goal of asthma?

A

Activate B2 adrenoceptors to relax airways but avoid B adrenoceptors else where in the body

240
Q

Describe the properties of salbutamol and salmeterol

A

Salmeterol - lower Kd for B2 compared to B1 therefore increased affinity- selective efficacy
Route of adminstration limits B1 affects
Salmeterol - longer acting no selective efficacy prevents b1 side effects by different affinty

241
Q

What is the problem of giving salbutamol in a drip to a patient with a heart condition?

A

No selectivity so causes increased heart rate by activation of B1 receptors and therefore reduces filling of coronary vessels leading to angina symptoms

242
Q

When are spare receptors often seen and why?

A

receptors that show catalytic activity as amplification in signal transduction pathway and response limited by poster receptor event

243
Q

What is the function of spare receptors?

A

Increase sensitivity allowing for response at decreased conc

244
Q

changing receptor number affects what?

A

Changes agonist potency - affects maximal response that can be induced

245
Q

With increased activity what happens to the number of receptors found on a cell membrane ?

A

Decrease

246
Q

What are partial agonists?

A

Drugs that cannot produce maximal effect even when full receptor occupancy

247
Q

Can a partial agonist be increased potent than full agonist?

A

Yes - depends on tissue and biological response

248
Q

When can a partial agonist turn into a full agonist?

A

Increased receptor number - still show low efficacy but sufficient receptors

249
Q

Give a use of partial agonist

A

Opoids
Morphine - full agonist
Buprenorphine - partial agonist - increased affinity but decreased efficacy provides adequate pain relief but decreases respiratory depression.
Addicts still get withdrawel symptoms

250
Q

What are the 3 types of antagonists?

A

Reversible competative antagonists
Irrervsible competative antagonist
Non competative antagonist

251
Q

Describe reversible competitive antagonists

A

Relies on dynamic equilibrium between ligands and receptors - increased conc increases inhibition
overcome by increasing agonist conc which causes a parralell shift to R of conc response curve
EG Naxolone for opoid respiratory depression

252
Q

Describe irreverisble competitive antagonists

A

Slow or no dissociation
Causes a parrallel shift to R of agonist conc response curve and at an increase conc supress maximal response - spare receptors filled by antagonist so not enough free receptors to elicit maximal response
EG Phenoxybenzamine - non selective alpha 1 blocker used in hypertension episodes of phenochromocytoma

253
Q

Describe non competative antagonists

A

Allosteric binding to receptor molecules - increase or decrease effect of binding of agonist

254
Q

Describe desensitisation

A

Loss of functional response usually reversible due to down regulation of receptors and uncoupling of receptor-effector molecules eg during repeated drug application

255
Q

Define tolerance

A

Diminishing effect of a drug due to prolonged repeat exposure - have to give increased amounts for same effect

256
Q

Define supersensitivity

A

Enhanced response of binding of agonist

257
Q

Define tachyphylaxis

A

Response to a drug gets smaller when a drug is given at high doses / repeatedly

258
Q

Describe homologous desensitisation

A

Receptor decrease its response to signal when agonist present at high conc

259
Q

Describe heterologous desensitisation

A

Prolonged stimulation to one agonist results in desenstisation to variety of agonists
Receptor is uncoupled from cascade

260
Q

Give some methods of desensitisation

A

Phosphorylation of receptor eg binding of adrenaliune to B adrenergic receptor activates G protein - while dissociated Gby subunit activates BARK a kinase which phosphorylates residues on carboxyl terminus of receptor
Receptor internalisation

261
Q

Define pharmacokinetics

A

What the body does to the drug

262
Q

What can changing receptor number do?

A

Changes agonist potency and affect maximal response

262
Q

Why does binding to spare receptor have no effect one 100% effectiveness been reached ?

A

Lack of ability post receptor binding eg ions or cascade working at maximal capacity

263
Q

What is orthosteric?

A

Binding act active site

264
Q

Give three ways that a drug is administered? How are they altered in the body?

A

Oral - goes through first pass metabolism which alter the drug
Parenteral- intravenous and intramuscular which goes straight into extracellular fluid
Topical - cream into the site

265
Q

Apart from administration what do drugs maker need to consider

A

Formulation - subset of oral administration

Compliance - liquid to children

266
Q

What is theraputic ration

A

Lethal dose over effective dose for half the population

267
Q

What does an incresed theraputic ratio lead to ?

A

Increased therpeutic window

268
Q

What is bio-avaliablity?

A

Proportion of drug reaching systemic circulation unchanged - affected by first pass effect
Only applies to thing that are administered orally
Sometimes measured as area under curve of orally taken in drug divide the injected one

269
Q

Describe first pass metabolism

A

May activate or not change drug but normally inactivated reducing the oral dose decreasing bioavaliability

270
Q

How can first pass metabolism be avoided ?

A

Changing administration route - eg GTN given sublingually

271
Q

Describe drug metabolism

A

Most by enzymes in the liver which are inducable and inhibitable by other enzymes

272
Q

How are drugs excreted?

A

Only free drug filtered by glomerulus- may be activate lay secreted by tubule cells
Passive reabsorption only occurs to non ionised - depends on drug pka and urging pH- increases blood conc
Aspirin overdose make the urine alkali to increase removal

273
Q

What happens to a drugs half life during renal failure?

A

Increased

274
Q

How are drugs transported in the body? What effect does this have on amount of response ?

A

Bound to carrier proteins such as albumin

Only the free unbound drug can interact with the receptor

275
Q

Why would you give larger concentrations of class two drugs? When is this used?

A 
Given at dose greater than number of albumin binding sites - allow more of the class 1 drug to be free in the blood leading to a greater response at a lower dose 
When class 1 toxic at high doses due to side effects 
When class I has a high affinity to albumin
276
Q

What type of drug is warfarin ?

A

Class 1 therefore must be careful with dose as narrow theraputic window

277
Q

Describe first order drug elimination

A

Rate of elimination is proportional to drug conc

Half life is constant

278
Q

Describe zero order drug elimination

A

Rate of elimination is contact because the enzymes are saturated -happens to all drugs at high doses
Must be very careful when administering 0 order drugs as conc will increase massively as no more can be removed

279
Q

Describe the parasympathic nervous system

A 
Rest and digest 
Craniosacral
Use Ach at both ganglionic neurones 
Long myelinated pre ganglionic fibres short unmyelinated  post ganglionic fibres
Ganglia located in tissues
280
Q

Describe the sympathetic nervous system

A

Fight or flight
Thoracolumbar
Preganglionic Ach and post ganglionic use NA
Short myelinated pre ganglionic fibres and long myelinated post ganglionic fibres
Ganglia in para vertebral chain

281
Q

What are the exceptions in the sympathetic nervous system

A

sweat glands and hair follicles are cholinergic
NANC transmitter may be released - non adrenergic non cholinergic
Sympathetic neurones to chromaffin cells in adrenal medulla are only preganglionic

282
Q

Describe nor adrenaline synthesis

A

Tyrosine , DOPA dopamine to adrenaline

Enzymes invoked tyrosine hydroxylase , DOPA decarboxylase and the Dopamine b hydroxylase

283
Q

Describe signal termination of nor adrenaline

A

Uptake 1 - by Na dependent high affinity transporters
Uptake 2- 5% escapes
Within presynaptic repackaged or degradaded

284
Q

What are NANC? Give some examples

A

Non adrenergic non cholinergic transmitters that may be co released with Ach or NA
Examples include- ATP, NO, 5 hydroxytryptamine and neuropeptides

285
Q

Describe the function of chromaffin cells

A

Found in the adrenal medulla - sympathetic nervous innervation leads to release of nor adrenaline into the blood. They are considered only to have a pre ganglionic neurone therefore use Ach

286
Q

What parasympathetic effects are there on the heart ? At what receptors?

A

Act at the atria on M2 receptors

Causing bradycardia and cardiac conduction velocity

287
Q

What parasympathetic effects are there on the lungs ? At what receptors?

A

Bronchial/bronchiolar contraction - M3

288
Q

What parasympathetic effects are there on smooth muscle ? At what receptors?

A

Increased intestinal mobility /secretion M3
bladder contraction and relaxation , Penile erection and ciliary muscle and iris sphincter contraction due to NO generation

289
Q

What parasympathetic effects are there on glands ? At what receptors?

A

Increased sweat/ salivary/ lacrimal secretion at M1 and M3

290
Q

What sympathetic effects are there on the heart ? At what receptors?

A

Atria and ventricles
Tachycardia and positive inotrophy
on B2 receptors

291
Q

What parasympathetic effects are there on smooth muscle ? At what receptors?

A

Arteriolar contraction/ venous contraction A1 or B2
Bronchiolar, intestinal and urinal relaxation B2
Bladder sphincter contracition B3
Radial muscle contraction - A1`

292
Q

What are the basic steps in neurotransmission?

A

1) uptake of precursors
2) synthesis of transmitter
3) vesicular storage of neurotransmitter
4) degradation of transmitter
5) depolarisation by propagated action potiental
6) Influx of ca in response to depolarisation
7) Exocytotic release of transmitter
8) diffusion to post synaptic membrane
9) interaction with post synaptic membrane
10) Inactivation of transmitter
11) reuptake of transmitter or degradation products
12) interaction with pre synaptic

293
Q

Explain how Ach is synthesised?

A

Enzyme choline acetyltransferase
From choline ( essential in the diet) and acetyl CoA in the cytoplasm.
Producing Ach and coenzyme A

294
Q

Explain how Ach is degraded ?

A

Enzyme - Acetyl cholinesterase

Produces- Acetate and choline

295
Q

At what points could drugs be used to inhibit Ach action?

A

Anticholinesterases
Depolarising blocking agents
Non depolarising blocking agents
Presynaptic toxins

296
Q

How do agents that interfere with cholinergic transmission usually act?

A

Interaction with cholinoreceptors or cholinesterase inhibitor to decrease rate of Ach degeneration

297
Q

Describe the treatment of glaucoma?

A

Pilocarpine applied in the form of eye drops .

Pilocarpine is a muscarinic cholinoceptor agonist

298
Q

Give some examples of some nicotinic cholinoceptor antagonists

A

Those that have preferential ganglion- trimethaphan

Neuromusclar blocking action - tubocurarine

299
Q

Describe and name some muscarinic cholinoceptor antagonists

A

Hyosine - anaesthetic premedication- decreases brochial and salivary secretions, prevents reflex bronchioconstriction , reduces any bradycardia induced by anaesthetic and sedative effect
Local application of poorly absorbed muscarinc cholinoceptor antagonist- used to treat bronchoconstriction in asthmatics
Homatropine - causes pupillary dilation and paralysis of accomadation - facilatating opthalmoscopic examination

300
Q

Give some function od cholinesterase inhibitors

A

Used to acutely reverse the effects of non depolarizing neuromusclar blocking agents used in anaesthesia, treatment of glaucoma and myasthenia gravis.
recently early treatment of alzheimers

301
Q

What is the rate limiting step in the synthesis of NA?

A

Tyrosine hydroxylase

302
Q

What allows the release of adrenaline into the blood?

A

Presence of phenylethanolamine N- methlytransferase in chromaffin cells

303
Q

What enzyme allows conversion from dopamine to NA? Where is it found?

A

Dopamine B hydroxylase

Within synaptic vesicles

304
Q

What do the vesicular transport systems recognise ? What does this allow for?

A

Dopamine and Nor adrenaline allowing reuptake and recycling.

305
Q

What are the likely side effects of non selective muscarinic Ach receptor agonist?

A

Decrease heart rate and CO
Increased bronchoconstriction and GI tract perstalsis
Increased sweating and salvation

306
Q

What is a variscosity? Where are they found?

A

Highly branching axonal network with numerous cell like bulges- varicosity- each of which is a specialised site for Ca dependent nor adrenaline release

307
Q

Outline the stages following an Ca dependent exocytosis release of NA

A

NA diffuses across the synaptic cleft and interacts with adrenoceptors in the post synaptic membrane to intiate signalling in the effector tissue
NA interacts with pre synaptic adrenoceptors to regulate processes within the nerve terminal
Only a small window to influence adrenoceptors as rapidly removed by noradrenaline transporter proteins

308
Q

What two enzymes are involved in metabolism of non taken up NA?

A

Monoamine oxidase

Catechol-O-methyltransferase

309
Q

How can presynaptic G protein coupled receptors regulate neurotransmitter release?

A

Inhibiting Ca dependent exoytosis
G protein By subunit inhibits specific types of voltage gated Ca channels reducing ca influx and neurotransmitter release

310
Q

What are the classes of drugs acting on adrenergic nerve terminals?

A 
a methyl tyrosine 
A Methyl DOPA
CarbiDOPA
Adrenergic blocking agents
Indirectly acting sympathomimetic agents 
Uptake 1 inhibitors
311
Q

Describe the mechanism of action of a methyl tyrosine

A

Competatively inhibits tyrosine hydroxylase - blocks synthesis of NA.
Used to inhibit nor adrenaline synthesis in pheochromocytoma

312
Q

Describe the mechanism of action of a methyl DOPA

A

taken up and converted into a methyl noradrenaline by DOPA carboxylase and dopamine B hydroxylase.
Accumulates in the synaptic vesicles - released by Ca mediated exocytosis but differs from NA as preferentially activates pre synaptic a2 adrenoceptors reducing transmitter release
Exploited in hypertension

313
Q

Describe the mechanism of action of carbiDOPA

A

Inhibits DOPA carboxylase in periphery but not in CNS

Used as part of treatment for parkinsons

314
Q

Describe the mechanism of action of adrenergic blocking drugs

A

Selectively concentrated in terminals by Uptake 1. They act via a variety of mechanisms, including a local anaesthetic action reducing impulse conduction and Ca2+ mediated exocytosis and repletion of NA from synaptic vesicles. Rarely used therapeutically because of severe side effects (postural hypotension).

315
Q

Describe the mechanism of action of uptake 1 inhibitors

A

Comprise an important class of therapeutic agents, the tricyclic antidepressants. These agents exert their therapeutic actiosn centrally and their possible peripheral actions (e.g. tachycardia and cardiac dysrhythmias) are unwanted side effects.

316
Q

What drugs act at cholinergic nerve terminals

A
  • Nicotinic Cholinoceptor Antagonists
  • Muscarinic Cholinoceptor Agonists
  • Muscarinic Cholinoceptor Antagonist
  • Cholinesterase Inhibitors
317
Q

Describe the mechanism of indirectly acting symohomimetic agents

A

Structurally related to noradrenaline - weak agonists at adrenoceptors
IASA recongised and taken up into synaptic vesicles where they cause leak of NA- displacement can leak into synaptic cleft by unrelated mechanism.
Extent to leakage greatly enhanced by inhibition of noradrenaline degrading enzyme MAO.

318
Q

Give some important uses of adrenoceptor agonists

A

selective b1 agonists - dobutamine- positive inotrophy and chronotrophic effect for use in circulatory shock (BUT prone to causing cardiac dysrythmias)
Selective B2 agonists - bronchoonstriction reversal in asthma
selective a1 agonist - nasal congestants - may be given in conjection with local anaesthetic injection to cause vasoconstriction and there slow spreading of anaesthetic
Selective A2 agonists - antihypertensive agents - through stimulation of inhibitory pre synaptic receptors which decrease NA release and centrally mediated action

319
Q

Give some important uses of adrenoceptor antagonists

A

A adrenoceptor antagonist - cause peripheral vasodilation in treatment of peripheral vascular disease
Not hypertension as cause postural hypotension and reflex tachycardia
Selective a1 adrenoceptor antagonists used in treatment of hypertension
B adrenoceptor antagonists- hypertension, cardiac dysrhythmias, angina and MI- possible side effects bronchoconstriction, bradycardia , cold extremities, insomina and depression.

ESA two revision (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions