Homeostasis 1 Flashcards
1
Q
What proportion of cell membrane is lipids?
A
42%
2
Q
What proportion of cell membrane is proteins?
A
55%
3
Q
What proportion of cell membrane is carbohydrates?
A
3%
4
Q
What primary function does the cell membrane function?
A
Divides IC and EC fluid
5
Q
What kinds of substances freely diffuse across the membrane?
A
Lipid soluble substances
6
Q
What kind of substances require transport proteins?
A
Small molecules and ions
7
Q
What kind of substances require endocytosis?
A
Large molecules
8
Q
What are the three fundamental methods of crossing the cell membrane?
A
Diffusion, transport proteins and endocytosis
9
Q
What are the three fundamental types of transporters?
A
Carriers, pumps and channels
10
Q
Why are carriers described as secondary active?
A
Reliant on primary active proteins that are reliant on ATP, i.e. they are 2 steps away from ATP
11
Q
What do pumps rely on?
A
ATP
12
Q
What is the most common kind of channel transporter?
A
Voltage gated
13
Q
Comment on the turnover and speed of channel transporters.
A
Very high turnover - million to 10 million ions per second
14
Q
What is the patch clamp technique used for?
A
Measuring currents across a very small region of the cell membrane
15
Q
Describe the patch clamp technique.
A
Pipette with 1µm tip attached to cell and filled with salt solution and silver wire. Wire attaches to reference electrode in EC space. Suction applied to create high resistance seal with the cell membrane, and currents are measured across that patch
16
Q
What else can the patch clamp technique be used for?
A
Measurement of the whole cell PD - enough suction can rupture the cell
17
Q
What are the drawbacks to the patch clamp technique?
A
Identification of channels is difficult, regulatory properties are unknown, physiological function is difficult to discern
18
Q
What equation defines protein channel regulation?
A
SEE PAD 5
19
Q
How do you measure Vm?
A
Insert electrode through PM containing salt solution that cannot leave; difference in voltage between solution and reference electrode outside of cell calculated as Vm
20
Q
What is the distribution of Na across the cell?
A
15mM IC; 150mM EC
21
Q
What is the distribution of K across the cell?
A
150mM IC; 5 mM EC
22
Q
What is the distribution of anions across the cell?
A
65mM IC; 0mM EC
23
Q
What maintains the K/Na distribution?
A
Na/K ATPase
24
Q
What does the restriction of anions IC allow?
A
Potential gradient to drive PM proteins
25
What two methods does Na/K ATPase contribute to Vm?
Direct - 20% - electrogenic transport protein that creates a loss of +ve charge; indirect - through IC K and Na changes
26
Define the Nernst equation.
SEE PAD 25
27
What is E-K?
minus 90.1 mV
28
What is E-Na?
plus 61 mV
29
What is Vm?
minus 70 mV
30
Define the Goldmann equation.
SEE PAD 26
31
What kind of disease is long QT syndrome and myotonia?
Channelopathies
32
What are the five stages that channelopathies can be interfered with?
Conduction, regulation, trafficking, processing, production
33
What do long QT syndromes lead to?
Arrhythmias and sudden death
34
What is the incidence of long QT syndrome?
1 in 10,000 to 1 in 15,000
35
How many forms of long QT syndrome are there?
7, possibly 8
36
What mutations cause long QT-1?
LOF KCNQ1
37
What are KCNQ?
K channels
38
What does LOF stand for?
Loss of function
39
What does GOF stand for?
Gain of function
40
Why doesn't LOF KCNQ1 stop all K transport?
More than one K channel, so K still moves, just takes longer to repolarise
41
What regulates KCNQ1?
KCNE1
42
What mutations cause long QT-5?
LOF KCNE1
43
What mutations cause LQT-2?
LOF HERG K channel
44
What mutations cause LQT-3?
GOF SCN5A Na channel
45
What mutations cause LQT-4?
LOF ankyrin B
46
What mutations cause LQT-6?
LOF KCNE2
47
What mutations cause LQT-7?
LOF Kir2.1
48
What is myotonia?
Muscle stiffness through hyper-excitability of skeletal muscle by delayed relaxation
49
What is the incidence of myotonia?
1 in 23,000 to 1 in 50,000
50
What causes myotonia congenita?
LOF CLCN1
51
What two types of myotonia congenita are there?
Thomsen's AD and Becker's AR
52
What does AD stand for?
Autosomal dominant
53
What does AR stand for?
Autosomal recessive
54
What is another name for paramyotonia?
K aggravated myotonia
55
What is another name for K aggravated myotonia?
Paramyotonia
56
What mutation causes paramyotonia?
GOF SCN4A
57
What is SCN4A?
Na-v 1.4
58
What is the MOA of paramyotonia?
Inactivation of gated Na channel, thus more Na enters muscle and depolarisation is prolonged
59
What is the treatment for paramyotonic CLC1 mutations?
Mexilitene
60
What is mexilitene used to treat?
Paramyotonia
61
What is the MOA of mexilitene?
Na channel blocker
62
What is the genetic inheritence of CF?
AR
63
What does CF stand for?
Cystic fibrosis
64
What is CF?
Disease of electrolyte transport in epithelial
65
What is the incidence of CF sufferers?
1 in 2500
66
What is the incidence of CF carriers?
1 in 20
67
What is the MOA of CF?
Problems with trafficking channels to the cell surface
68
What six organs are affected by CF?
Airways, liver, pancreas, small intestine, reproductive tract and skin
69
How are the airways affects by CF?
Clogging and infection
70
How is the liver affected by CF?
Blockage of small bile ducts and problems with liver function in 5%
71
How is the pancreas affected by CF?
Blockage of ducts prevents secreation of digestive enzymes in 65%
72
How is the small intestine affected by CF?
Obstruction due to thick content in 10% of newborns
73
How it the reproductive tract affected by CF?
Absence of vas deferens in 95% of males, thus infertile
74
How is the skin affected by CF?
Excess secretion of NaCl via sweat glands
75
What does NBD stand for?
Nucleotide binding site
76
What is the R site on a channel?
Regulatory part
77
How many CFTR mutations have been identified?
1600
78
How many CFTR mutations can cause CF?
1000
79
Where are 70% of patients' CFTR mutations?
Delta F508
80
What is the lung pathology of CF?
Viscous muscous airway, recurrent bacterial infections, antibiotic resistance, inflammation, tissue degeneration, common cause of death
81
Outline normal NaCl secretion in upper airway.
SEE PAD 27
82
How does the normal mucuous protective layer form?
Water flows past mucosal cell layer with Cl flow
83
When was Liddle's syndrome first described?
1963
84
What is the inheritence of Liddle's syndrome?
AD
85
What characterises Liddle's syndrome?
Na retention, fluid retention, hypertension, hypokalaemia, metabolic alkalosis, low renin and aldosterone levels
86
What is the MOA of Liddle's syndrome?
Increased Na reabsorption, increased H2O reabsorption, increased K secretion, increased H secretion
87
What causes Liddle's syndrome?
Mutation in the COOH tail of ENaC leading to insertion, but not endocytic removal from the apical cell surface
88
What is the incidence of malignant hyperthermia?
1 in 10,000 to 1 in 50,000
89
What is the genetic inheritence of malignant hyperthermia?
AD
90
What is malignant hyperthermia?
Abnormal response to anaesthesia
91
What is the mortality rate of malignant hyperthermia if not treated?
80%
92
What is the mortality rate of malignant hyperthermia if treated?
10%
93
What is tachypnea?
Rapid breathing
94
What are the symptoms of malignant hyperthermia?
Tachypnea, low plasma O2, high plasma CO2, tachycardia, hyperthermia, rigidity, sweating, shifts in BP
95
What happens to sufferers of malignant hyperthermia if not treated?
Respiratory and lactic acidosis, muscular rigidity, muscle breakdown, severe hyperkalaemia, cardiac and neuronal hyperexcitability
96
What is the physiological reason for malignant hyperthermia?
Uncontrolled muscle contraction, excessive ATP hydrolysis, hypermetabolic state muscles
97
What is RyR1?
Skeletal muscle ryanodine receptor
98
What does MH stand for?
Malignant hyperthermia
99
What mutations cause MH?
RyR1 GOF - increases P-0 of Ca channels
100
What is the P-0 of a ion channel?
Opening probability
101
What anaesthetic triggers a malignant hyperthermic attack?
Halothene
102
What does GOF mutation to RyR1 do?
Increases sensitivity to halothene
103
What is the treatment of MH?
Dantrolene - inhibits RyR1, IV hydration, diuretic - stops kidney damage, NaHCO3 - counter acidosis, hyperventilation
104
What is episodic ataxia type II?
Irregular uncontrolled muscle contraction
105
What is the genetic inheritence of episodic ataxia type I and II?
AD
106
What mutation causes episodic ataxia type I?
KCNA1 (K-v)
107
What mutation causes episodic ataxia type II?
CACNA1A (Ca-v)
108
When is the average onset of episodic ataxia type I?
20-30 years
109
When is the average onset of episodic ataxia type II?
Child to teens
110
What symptoms characterise episodic ataxia type I?
Ataxia, dizziness
111
What symptoms characterise episodic ataxia type II?
Ataxia, vertigo, nausea, headache
112
How long are episodic ataxia type I attacks?
Brief
113
How long are episodic ataxia type II attacks?
30mins - 24hours
114
Where is CACNA1A?
Purkinje cells, granule cells, cell bodies, cerebellum, exocytotic NT release
115
What is used to treat episodic ataxia?
Acetazolomide
116
What type of drug is acetazolomide?
Carbonic anhydrase inhibitor
117
What is acetazolomide used to treat?
Episodic ataxia
118
What causes the predominant symptoms of influenza?
Respiratory pathogens disturb fluid balance in the respiratory tract
119
How do viruses distrupt the fluid balance in the respiratory tract?
Knock out Na channels
120
What proteins are on the basolateral surface of the lining of the respiratory tract?
NKCC2, K/Na ATPase, ROMK
121
What is tetrodotoxin?
Kind of neurotoxin - guanidium neurotoxin
122
What is guanidium neurotoxin also known as?
Tetrodotoxin
123
Characterise the potency of tetrodotoxin.
10,000 times stronger than cyanide - nM levels required for death
124
Where is tetrodotoxin found?
Produced by marine bacteria - held in invertebrates, amphibians and fish
125
How can tetrodotoxin be accidentally ingested?
Incorrect Fugu preparation - pufferfish
126
What marine creatures commonly have tetrodotoxin in their bodies?
Pufferfish, blue-ringed octopus
127
What are the symptoms of tetrodotoxin ingestion?
Numbness of lips and tongue, facial parasthesia, headache, nausea, dizziness, diarrhoea, vomiting, increased paralysis, respiratory paralysis, death in 20mins to 8 hours
128
What does TTX stand for?
Tetrodotoxin
129
What is the treatment for tetrodotoxin ingestion?
Mechanical ventilation - no anti-venom because TTX binds too strongly
130
What does TTX act upon?
Na channel
131
What does the TTX inihibtion of Na channels cause?
Failure of neurotransmission, reduction in release of NT, loss of sensation and muscle paralysis, respiratory paralysis
132
Outline the variable sensitivy of the body to TTX.
Brain + muscle - sensitive, heart - insensitive; change Na-v 374 from cysteine to tyrosine in the heart leads to sensitivity
133
What three breast cancer metastatic genes have been identified?
Cell cycle markers, adhesion markers, motility factors
134
What is the difference in Ca concentration IC and EC?
10,000 fold - 100nM indside, 10mM outside
135
What keeps the Ca concentration IC and EC stable?
Ca/Na exchanger, Ca ATPase
136
Why is it important that IC Ca concentrations are kept so low?
Important secondary messenger, so too much would result in a lack of sensitivity
137
What does the Ca/Na exchanger do ionically?
Swaps Na outside for Ca inside - 3Na:1Ca
138
What does the stoichiometry of the Ca/Na exchanged mean?
When at equilibrium and combined with membrane potential, the 10,000 fold Ca gradient is maintained
139
What is NCX?
Na/Ca exchanger
140
What three kinds of Ca pump are there?
PMCA, SERCA, SPCA
141
What is PMCA?
Ca ATPase
142
What is SERCA?
Ca ATPase
143
What is SPCA?
Ca ATPase
144
What does PMCA stand for?
Plasma membrane Ca pump (ATPase)
145
What does SERCA stand for?
Smooth endoplasmic reticulum Ca pump (ATPase)
146
What does SPCA stand for?
Secretory pathway Ca pump (ATPase)
147
What does PMCA do?
Pump Ca out of the cell
148
What does SERCA do?
Pump Ca out of the cytoplasm and into SER
149
What does SPCA do?
Pump Ca out of the cytoplasm and into Golgi apparatus
150
What four channels are involved in Ca signalling?
VOCC, ROCC, SOCC and mechanically activated Ca channels
151
What does VOCC stand for?
Voltage operated Ca channel
152
What does ROCC stand for?
Receptor operated Ca channel
153
What does SOCC stand for?
Store operated Ca channel
154
Where are VOCC found, and how are they activated?
Excitable cells, activated by depolarisation
155
Where are ROCC found, and how are they activated?
Secretory cells and nerve terminals, activated by binding of agonist
156
How are SOCC activated?
Activated following the depletion of stores
157
Where are mechanically operated Ca channels found, and how are they activated?
Any cells that respond to deformation - activated by that deformation
158
What does failure to migrate and aggregate cells lead to?
Cell, tissue and organism dysfunction/death
159
What are cadherins?
Calcium dependent cell surface molecules
160
How many cadherins do L cells express?
2
161
How were cell adhesion molecules discovered?
Monoclonal anti-bodies
162
Describe the structure of cadherins.
Monomeric integral membrane glyco proteins, 720-750 a/a
163
What happens to cadherin when Ca binds?
Change from floppy to rigid
164
What link cadherins to cytoskeleton?
Catenins
165
What do catenins do?
Bind cadherins to the cytoskeleton
166
Where is e-cadherin expressed?
Early embryo
167
Where is n-cadherin expressed?
Replaces e-cadherin in the neural tube
168
What do selectins do?
Bind specific carbohydrate groups
169
Are selectins Ca dependent?
Yes
170
What are selectins involved in?
Neutrophil trapping
171
What is diapedesis?
Ability of white blood cells to squeeze through the capillary wall
172
How are selectins involved in neutrophil trapping?
P-selectin slow white cells down, others drag it down
173
Describe Ca INDEPENDENT CAMs.
Numerous, N-CAMS are the major form (neural)
174
What are Ca independent CAMs involved in?
Homophilic, ECM and cell binding
175
How are Ca independent CAMs generated?
From a single gene, aternative forms deriven by splicing and post-translational glycosylation
176
Describe the structure and classes of integrins.
Dimers - 16 alpha and 8 beta types
177
What do integrins do?
Bind the cytoskeleton, causing outside-in or inside-out activation of signalling pathways
178
Are integrins Ca dependent?
No
179
What does FAK stand for?
Focal adhesion kinase
180
What is FAK regulated by?
Ca binding
181
What does FAK do?
Recruits/activates multiple tyrosine kinases to inhibit focal adhesions
182
When is FAK activated?
On formation of focal adhesions
183
In what important pathway does FAK function?
Anoikis - attachment dependent cell death
184
What is mammalian cell motility mainly based upon?
Actin
185
What is the cellular cortex?
Layer just inside the PM that convey structural support
186
What happens during cell migration?
Cortex aids PM tension, signals cause local actin reorganisation, cortex transmits tension, cell polarity emerges, leading edge toward signal, myosin II aids tail retraction
187
What two features comprise the leading edge?
Ruffling and retrograde actin transport
188
Describe leading edge ruffling.
Forms in front and 'crashes' backwards, acts like arms grabbing monkey bars
189
What is responsible for nucleation of actin filaments?
ARP complexes
190
Which end of actin filaments is associated with a cluster of proteins?
Minus end
191
What does the minus end of actin filaments serve as?
Seam for further growth
192
What angle do actin filament branches cross link?
70 degrees
193
Along with ARP compexes, what else congregates at the leading edge?
Cofalin and capping proteins
194
What form low density focal adhesions?
rac1, cdc42
195
What form high density focal adhesions?
RhoA, actin-myosing interaction
196
Characterise low density focal adhesions.
Immobile
197
Characterise high density focal adhesions.
Sliding in the membrane
198
Name three motility signals.
Netrins - soluble; CAMs/ECM - insoluble; Fibronectin/crest cells
199
Define the equation for water flux into/out of a cell.
SEE PAD 37
200
Why is cell volume important?
Structural integrity + cellular protein functioning
