Neurons (Cahill Stuff) Flashcards
1
Q
What is the Davson- Danielli model
A
That cell membranes had a 3 layered structure: protein, bilayer, protein
Based on electron micrograph a
2
Q
What happened in 1966
A
Branton used freeze-fracturing to split cell membranes and proteins were seen through the fracture plain
3
Q
Experimental evidence for fluid mosaic model
A
Distinctly Labelled mouse and human proteins were combined in a hybrid cell, the surface proteins became intermingled
(Frye and Edidin, 1970)
4
Q
What are the two main kinds of non covalent interactions in the fluid mosaic model
A
Hydrophobic and hydrophilic
5
Q
What does the value of the potential difference across a membrane reflect
A
The concentration of unbalanced charge
6
Q
Is the inside of a cell more or less negative
A
Inside is more negative
7
Q
How does a cell membrane act as a variable resistor
A
It contains channels that allow a flux of ions under specific conditions
8
Q
How is electrical potential across a membrane measured
A
A micro electrode is inserted within the neuron (usually in the soma) and a second is placed in the extra cellular fluid
9
Q
By Whom and when was the ionic basis of resting potentials put forward
What was he aware of
A
Bernstein, 1902
That intracellular K> extra cellular
And that the membrane was more permeable to K than any other ion
10
Q
What is the equilibrium potential
A
A balance between concentration gradient and charge gradient
11
Q
What can’t electrodes do that means the Nernst equation is needed
A
Can’t tell us which ions account for the charge recorded
12
Q
What are the assumptions in the Nernst equation
A
For a single ion
Completely permeable membrane to that ion
Ion in equilibrium
13
Q
What is the Nernst equation
A
E=RT
-— x ln([ref]/[test])
zF
14
Q
Does reference= out or in
A
Out
15
Q
What is Nernst equation simplified to at room temperature and at body temperature
A
58xlog([out]/[in])
Body: 61.5log([out]/[in])
16
Q
How did Hodgkin and Horowicz realise other ions contribute to the potential
A
At high [K] the results agreed with the Nernst equation but at lower concentrations, the results deviated
17
Q
Give the Goldman Hodgkin Katz equation
A
RT Pk[out]+PNa[out]+PCl[in]. — x ln ———————————
F Pk[in]+PNa[in]+PCl[out]
18
Q
What is the pump ratio for K and Na ions In the K/Na pump
A
3 Na ions are pumped out for every 2 K ions pumped in
19
Q
What does the Na/K pump require and what can it be describe as
A
Hydrolysis Of ATP
Electrogenic
20
Q
What is the equivalent of a battery in a neuronal circuit
A
Na/k pump
Stored potential that is maintained
21
Q
What is the equivalent of a resistor in a neuronal circuit
A
Ion channels
Prevent or allow flow of ions in and out of a cell
22
Q
What is the equivalent of a capacitor in a neuronal circuit
A
Cell membrane
The charge separation across it
23
Q
Hyperpolarising current pulses only ______ changes in membrane potential
What does this mean
A
Passive
They decay over time
24
Q
Small depolarising pulses elicit only _____ responses
A
Passive
25
When does a depolarising current produce an action potential
If it meets or exceeds a threshold, hence why they are all or nothing events
26
What does increasing the strength of a current do for an action potential
No effect on amplitude
| Number of spikes increase
27
What happens if you apply a voltage to a capacitor
What happens when the voltage is removed
It begins to store energy until it reaches maximum capacity and stays there
The capacitor discharges it’s voltage across the resistor until it has been fully discharged
28
What happens if a circuit has a resistor but no capacitor
When power is applied the voltage but change to its steady state value and when removed it would then drop to zero immediately
29
How does the capacitor resist drastic changes
It takes time to charge and discharge
30
What does τ (tau) measure
The time constant
| How quickly the neuron’s potential decays back to the resting state
31
How long is τ exactly
How long it takes a potential to get to 1/e of its original value
(63% of original value)
32
What equation describes the rise of voltage
V= Vmax(1-e^(-t/τ))
33
What equation describes the decay of voltage
V= Vmax x e^-t/τ
34
τ=?
Rm x Cm
35
What are the 2 major sources of resistance ions need to overcome in the axoplasm
Fibre length
| Lack of membrane resistance (too much leaking)
36
What is the length constant
λ
| An index of how well a sub threshold potential will spread along an axon as a function of distance
37
What does it mean to have a length constant of 1mm
1mm away from the axon cell body, 37% of the voltage remains
38
What is the actual equation for the decay of the potential with distance
V=Vmax(e^-x/λ)
39
What actually does λ=
Why can Ro be ignored
λ= sqrt (Rm )
(———- )
(Ro + Ri )
Ro<<
40
What ion is the membrane of a resting neuron most permeable to ?
K
41
What did Bernstein suggest about an action potential
What did the peak of the AP represent here then
Who noticed he was wrong
Due to a loss of membrane selectivity
The point of maximum conductance so would approach 0 mV
Cole and Curtis (1939)
42
How does capacitance change in an AP
It doesn’t
43
How did Hudgkin and Huxley experiment with APs originally
What did they observe
Modified the concentration of sodium by adjusting the concentration of salt water
The AP and overshoot became slower the more they reduced the Na
44
What did Huxley’s calculations about Na predict
The peak AP amplitude would track the Na equilibrium potential
45
How does improving insulation improve passive current flow
Reduced leakage
46
How does myelin affect the long motor neuron in the leg, speed wise
Without: speed= 1m/s
With: speed= 10-100m/s
47
What do the Glia do in nodes of Ranvier
Secrete specialised proteins that recruit Na channels to the node
48
What were Rushton’s predictions relating myelin and diameter
Myelinated: velocity is proportional to diameter
Unmyelinated: velocity is proportional to the square root of the diameter
49
What was the general rule of thumb that Erlanger and Gassers discovered in the 1920-30s
Larger diameter neurons are heavily myelinated, have low thresholds and are rapidly conducting
Unmyelinated have high thresholds and conduct slowly
50
Name some symptoms of MS
Dizziness, visual problems, headaches, neurological problems that persist for days then remittance
51
What happens due to demyelination in MS
Conduction is slowed and Na channels spread outward from nodes
52
How does a current clamp work
Experimenter injects a current in a ‘step’ fashion and measures how it impacts the membrane potential using a voltmeter and amplifier
Can be used to look at subthreshold stimulation forms of passive membrane currents
53
What was Hodgkin’s hypothesis concerning conductance of Na
Why Na
At a certain membrane potential, conductance (g) of Na increases
At resting potential thete is a high driving force acting on it
54
What does the voltage clamp amplifier do
Clamps the membrane potential at a set level and can detects the difference in current that needs to be injected to stabilise that level
(This required current is proportional to the conductance according to Ohm’s law)
55
What did H and H record from voltage clamp experiment
As the membrane was depolarised there was an inward [Na] dependant current
K conductance was found to lead to a time dependent outward current
56
How can the change in current with PD by shown
What drugs will change this graph
Am I-V curve
Any treatment that alters ionic conductance will alter its shape and slope
57
What can the slope of the I-V curve be used to calculate
Conductance
58
When does the IV curve pass through the voltage axis for a channel specific to ion X
At X’s Nernst equilibrium potential
59
What did the toxin TTX demonstrate
Why
Slow outward current was mediated by K
It blocks Na voltage gated channels
60
When are leak and gated channels important
Leak- to set resting potential
| Gated- in active changes
61
In a channel how many helices are in each subunit
Which form the pore
Which segment is charged and how do prevalent models suggest this moves upon depolarisation
6 transmembrane domains
S5&6
S4 - translocated from inside to outside the cell
62
Describe the helical screw model
Depolarisation causes S4 to rotate and twist up through membrane, changing the exposure of charges from the intra- to extra cellular solution
63
Describe the paddle model
S4 makes a large translation such that the most extra cellular charge goes from exposed to the extra cellular medium in the open state to completely buried in the bilateral in the closed state
64
What happens when the channels open upon depolarisation
Initially a few Na VGC open, increasing the amount of Na entering the cell, continuing to depolarise the membrane, triggering more Na VGC to open
65
When do Na VGC become inactive
It is time dependent- they are inactive after a set time from the VGC opening
The cell is now impermeable to Na, contributing to the refractory period
66
When are the Na VGC closed
When the membrane repolarises
67
Why is an action potential self supporting
Positive feedback loop of Na VGC opening. This also contributes to the all or nothing quality
68
What is the delayed rectifier
The Na VGC take 1ms to open upon depolarisation. This delay and the fact that K conductance serves to rectify the membrane potential.
This delay regulates the relative refractory period
69
What does the refractory period do
Limits number of APs in a given nerve per unit time and prevents back propagation of APs
70
What do TTX and TEA stand for and what do they do
TTX- tetrodotoxin
- binds to and blocks the Nav channels
TEA- Tetraethylammonium
- targets Kv channels
71
What is a channelopathy
Disease caused by disturbed function of ion channel subunits or the proteins that regulate them
72
What is myokymia
Reduced activity of K channels which delays AP repolarisation and lowers threshold, producing abnormal spontaneous AP generation
73
What is myotonia
Mutations in Na channels cause abnormal tendency for channels to open later or more persistently after depolarisation
Residual Na entry reinitiates the cycle of depolarisation
74
What is a Gap Junction
They are formed when 2 cells in close proximity that have channels allowing the propagation of an impulse almost directly
75
How are gal junctions structured
Built from 6 connexin subunits that comprise one connexon, then two connexons comprise one gap junction
76
2 advantages of electrical transmissions
Speed
| They favour synchrony when firing
77
Advantage of chemical transmission
Allows for more specificity
78
When and how did Dale shoe transmission could be chemical
1913
Injecting acetylcholine into a cat heart, inhibiting the heartbeat
A purified substance produced the same effect as parasympathetic nerve stimulation
79
Describe Ringer’s heart experiments
2 beating frog hearts isolated in containers of Ringer’s Solution
The vagus nerve (PNS) was stimulated in heart A, slowing its beat. Fluid from A moves to B, slowing the beat of heart B
80
What did Ringer’s experiments show
A soluble substance released by the vagus nerve modulated heart rate, which he called Vagusstoff but is actually ACh
81
Where are NT synthesised and stored
In the axon cytosol
Stored in synaptic vesicles
82
What happens when an impulse reaches a presynaptic terminal
Depolarisation causes opening of VG Ca channels
| Then vesicles can fuse with the presynaptic membrane and release their load
83
How and why are intercellular [Ca] levels kept low in neurons
So there is a strong driving force for it to enter once channels open
Transporters and pumps are recruited
Eg Na/Ca exchanger and Ca pumps
84
How is the VG Ca channel deactivated
Ca dependant inactivation site providing negative feedback to close the channel when [Ca] increase
85
What do SNARE proteins do
They’re on the synaptic vesicles and plasma membrane, and form a complex. This acts like a zip, bringing together the two membranes.
Ca then binds to synaptotagmin causing the cytoplasmic region of this protein to insert into the plasma membrane, bind to SNAREs and catalyse fusion and exocytosis
86
Do neurons need to recover vesicles
Yes
| They are recovered via endocytosis and the recycled vesicles is refilled with NT
87
What is Dale’s principle
A given neuron produces only one type of neurotransmitter (now disproved as co-transmitters, nerve terminal with multiple NTs, have be shown to exist)
88
For ACh in a NMJ, give the following:
a) synthesis
b) vesicles
c) Release
d) action
e) inacitvation
a) ChAT
b) Vesicles
c) Ca Dependant
d) nAChR
e) AChE
89
What are ionotrophic receptors
Ligand gated channels
90
Give an example of metabotrophic receptors
GPCRs
91
Give an important specialisation of the NMJ
It’s size- it is one of the largest synapses in the body
92
How does the motor end plate increase surface area
It has many folds
93
Give the resting potential and threshold of the motor end plate
- 100mV
| - 65mV
94
Give the experiment that shows that the presynaptic signal for full EPPs is Ca dependant
If NMJ is bathed in a solution of low [Ca], stimulating the neuron evokes EPPs reduced to the size of MEPPS
95
How could you show post synaptic signals are dependent on the nicotinic subtype of AChR
The antagonist, Curare, can reduce the EPP
96
What type of receptor are NAChR in the NMJ
What about in the heart
Ionotropic
Muscarinic AChR
97
When is the membrane potential ~0mV
When it is equally permeable to Na and K ie when many channels are open
98
What happens if membrane potential is <0mV before ACh was applied
What do you call the critical value when the flow direction changes
The direction of flow through ACh-gated ion channels is inward and vice versa
Reversal potential (which is 0 in this case)
99
What is driving force
How different the membrane potential is
| Vm-Erev
100
Are nAChR permeable to K or Na
What does conductance depend on
Both
How many channels are open which depends on [ACh]
101
What is the Quantal Transmission Hypothesis
Give its two main observations
EPPs are made of individual units, each equivalent of an MEPP
1. NT is released in multimolecular packets
2. Response EPPs fluctuate in steps of unit size corresponding to the size of mEPP
102
What is a simplistic way to determine the possible quantal content of an EPP
If you divide an EPP by an mEPP
103
How did Katz analyse the frequency of occurrence of MEPPs with respect to amplitude
Poisson Statistics
104
What is myasthenia Gravis
How are MEPPs affected
A chronic autoimmune neuromuscular disease that targets the nAChR, disrupting how the cells respond to synaptic transmission
Their amplitude is Greatly reduced
105
How do you treat myasthenia gravis
AChE inhibitors to prolong ACh activity
106
Are post synaptic potentials bigger in the brain or in the NMJ
Why
Brain PSPs are much smaller
In the CNS, PSPs can be fast acting and short-lived, triggered by iontropic receptors or slow and long lasting driven by metabotropic receptors
107
How can you measure the current produced by an EPP
Patch Clamp which measures discrete patches of membrane and the channels there-in
108
How do patch clamps work
The transmembrane potential is controlled by the patch clamp amplifier, the extra cellular fluid is considered the “ground/reference”
109
What is the outside-out patch
What does this allow
A configuration of the patch clamp where the extra cellular surface is on the external side of the pipette tip
Study of drug action on receptor surface
110
What can single channel recordings with the patch clamp allow
Study of unitary conductance and kinetic behaviour of ionic channels
This has shown that individual channel opening and closing are sudden, all or nothing events, triggered by ligand binding causing a conformational change to another
111
What muscle is contracted in the knee jerk reflex and what causes it
What kind of reflex is it
Quadriceps femoris
Hitting the patellar tendon
Protective reflex
112
How does hitting the patellar tendon cause a reflex action
The pressure stretches the muscles spindles causing contraction
113
What does an intact knee jerk indicate
What is the reflex arc
Integrity of the L2-L4 vertebral segments
Sensory efferent neurons project through dorsal root ganglion and synapse directly with the effector extensor motor neuron that projects back to the quadriceps muscle
114
What muscles are indirectly affected by the knee jerk reflex
The hamstring is inhibited by inhibitory interneurons which is necessary to avoid both muscles contracting simultaneously against each other
115
Are post synaptic potentials active
No they decay exponentially
116
What does the magnitude of a PSP depend on
The number of open ion channels which in turn depends on amount of NT released
117
How do the EPSP and ISPS act
EPSP -brings a membrane potential closer to threshold
IPSP - hyper-polarises the cell away from threshold
118
What did Brock notice about IPSP’s in the 1950s
Reversal only occurred when intracellular microelectromechanical contained KCl, suggesting Cl- is necessary for reversal
119
What is released from the presynaptic terminal of the sensory neurons in the extensor motor neuron of the patella reflex
What does it bind to
Glutamate
AMPAR
120
What does AMPAR activation lead to
Depolarisation of post synaptic cell via conduction of cations like a ligand gated ionotropic receptor
121
What do glycine receptors conduct?
Are they voltage gated?
Conduct Cl- and therefore lead to hyperpolarisation
No they are ligand gated ionotropic receptors
122
Is temporal summation active
It is strictly passive
123
What is the spatial summation influenced by
The space constant
124
What is equilibrium potential of an ion
The voltage that would occur if the membrane were fully permeable to that ion
125
What determines the threshold for an action potential
The sodium current exceeding the outward potassium current
126
What is the greatest delay at the NMJ
Ca2+ accumulation
127
Which band shorten during contraction
A stayed the same length H and I bands shorten
128
What are the effects and noradrenaline on the heart
Phosphorylation of phospholamban, troponin I and phosphorylation of calcium channels in the p.m.
129
What is the most important factor influencing brain bloodflow
Metabolic autoregulation
130
What determines maximum expiratory flow rate primarily
Elastic recoil of the lungs
131
What regulates alveolar ventilation when breathing normal air at sea level
PCO2
132
Contraction of the diaphragm and intercostal muscles does what to intrapleural pressure
Intrapleural pressure becomes more negative
133
How do glucose, galactose, and fructose cross the luminal border of the small intestine
Glucose and galactose: SGLT1
Fructose: GLUT5
All exit via GLUT2
