week 11 Flashcards
1
Q
what is ohms law
A
Movement of a dissolved, charged particle - i.e. an ion - across a
lipid membrane depends on:
▪ The charge of the particle
▪ The difference in distribution of charges across the
membrane – this separation in charges is represented by
voltage
* Voltage is a type of potential energy → how much work it
takes to move a charged particle through an electric field
▪ The permeability of the membrane to the charged particle
2
Q
Ohm’s law is most
useful when thinking about
A
unequal distributions of
charges very close on either
side of a membrane
3
Q
The Nernst potential is the membrane potential at
which the ……
A balance is reached between?
A
inward and outward movement of an ion
through a channel is balanced and equal
- The diffusional force (movement of an ion down
its concentration gradient)
▪ The electrical force (attraction or repulsion based
on the charge of the ion and the charge across the
membrane)
4
Q
Diffusional forces and electrical fields are very small at
A
large distances
5
Q
what does nernst potential not include?
A
- flow of ions (current) or the
resistance of the membrane to flow…
▪ It describes the energy gradient
6
Q
the electric field declines very rapidly as charges are separated by
A
distance
(ohms law)
7
Q
what is needed for nernst potential
A
60 mvl / the charge and valence of P (anions are negative)
log 10
= ratio of intracellular:extracellular concentrations of X
Describes the voltage across a membrane that is
permeable to X given the ratio of [X] inside:outside
8
Q
the ions …. to the membrane have the most effect on nernst potential
A
closest
9
Q
At rest, neurons typically have a membrane potential that is close to the Nernst potential for
A
K+
10
Q
The membrane
potential of any cell
depends on:
A
- The relative
permeability of
the membrane to
each ion - The concentration
of the ion on
either side of the
membrane
11
Q
If the membrane potential is close to the Nernst
potential of a particular ion, it usually means that
A
the membrane is more permeable to that ion
12
Q
The membrane potential is about …. in many neurons
A
-75 mV
13
Q
Why is the membrane potential of a neuron close to, but not the same, as the equilibrium (Nernst) potential for K+?
A
because there are other ions
14
Q
what is the concept of the Goldman Field equation
A
that the concentration of one electrolyte has effects on the others
15
Q
The potential across the membrane depends on
A
concentration gradients and the permeability (or its
inverse, the resistance) of the membrane to each ion
16
Q
Channels are often
A
dynamic
-They can open or close in response to a variety of stimuli…
▪ which means membrane permeability and the membrane
potential can change, often very quickly
17
Q
what are the main four types of channels
A
- Voltage – voltage-gated channels
▪ Stretch or mechanical deformation – mechanoreceptors or
osmoreceptors
▪ Intracellular messengers
▪ Extracellular messengers – ionotropic receptors
- A ligand binds to a receptor which is also a channel –
binding opens the channel, and allows an ion across the
membrane
18
Q
An action potential Requires
A
- the presence of sodium voltage-gated channels
(or sometimes calcium voltage-gated channels)
▪ Relies on positive feedback
▪ Always results in a membrane voltage change that is the same size
▪ Occurs very quickly – the membrane becomes more
positive (depolarized) in a matter of milliseconds
19
Q
Where do action potentials occur?
A
The axon hillock, the axon (or in myelinated axons the nodes of Ranvier) and the synaptic terminals possess a large population of sodium voltage-gated channels (Na+ VGC) in the membrane
K+ VGC are also present in these areas – they help to
quickly terminate the action potential
20
Q
…. starts an action potential …. ends an action potenial
A
sodium
potasssium
21
Q
… Na+ out … K+ in
A
3
2
22
Q
K+ concentrations are …inside the axon, and ….outside
A
high
low
23
Q
K+ is high inside the axon, therefore ..
A
it diffuses out
24
Q
what is the resting membrane potential
A
-70mV
25
what helps to keep the resting membrane potential
Na/ K+ATPase pump
26
what is depolarization
The inside of the axonal membrane becomes more
positive, and a Na+ VGC opens
▪ channels are opened by more positive charges inside
membrane
▪ threshold = membrane potential at which all Na+ VGC will
end up opening (~ -55 mV)
leads to other Na+ VGC opening, eventually all open
- positive feedback, Na+ diffuses into the cell, making
membrane more positive, allowing more Na+ in
Inside of the axon becomes completely depolarized
▪ diffusion gradient (high Na+ outside, low inside) as well as
electrical force (inside negative) drives Na+ into the cell
* K+ VGC open, Na+ VGC close after ~ 1 msec
27
what happens during repolarization
* Na+ VGC are closed, no further Na+ entering the axon
K+ rapidly leaves the axon
▪ high K+ inside axon and positive charge inside the membrane
strongly drive K+ out
▪ K+ VGC and regular K+ channels are both open, allowing rapid
K+ exit
Na+ VGC are ready to re-open:
▪ when membrane potential is -70 mV (repolarization)
▪ after they’re “unlocked” (1 – 2 msec after closing)
28
what are the two gates of action potenials
The activation gate – this gate opens as soon as threshold is
reached (i.e. the membrane depolarizes to -55 mV)
The inactivation gate – this gate closes very soon after the activation gate opens, after Na+ has rushed into the cell
* The inactivation gate will not open again unless:
▪ 1-2 msec has passed since it has closed (it’s “locked”)
▪ The cell membrane becomes inside-negative again
(repolarized)
29
The potassium voltage-gated channel does not have an inactivation gate – it opens when the cell ......., and closes once the cell is .............
depolarizes
inside-negative again
It is slower to open than the sodium voltage-gated channel
30
what is the absolute refractory period
* Inactivation gate of
the Na+ VGC is
closed
* Another action
potential is
impossible until this
gate opens
31
what is the relative refractory period
Inactivation gate is
open, activation gate
is closed for the Na+
VGC
* The cell is
hyperpolarized – the
membrane potential is
lower than resting
membrane potential
* A larger stimulus is
necessary to reach
threshold
32
what are the actions of a action potential
All-or-none events
▪ Begin when a threshold voltage (usually 15 mV positive to resting
potential) is reached
▪ There are no “small” or “large” APs – each one involves maximal
depolarization → all Na+ channels open once threshold is reached
* Initiated by depolarization
* Have constant amplitude
▪ Action potentials don’t summate – information is coded by
frequency, not amplitude
▪ the size of the depolarization stays the same size no matter how far
it travels along axon
* Have constant conduction velocity along a fiber
▪ Fibers with a large diameter conduct faster than small fibers.
* Myelinated fiber velocity in m/s = diameter (um) x 4.5
* Unmyelinated fiber velocity in m/s = square root of diameter
(um)
33
why does myelin increase conduction speed
34
what is continuous conduction
no jumping, every channel has to open, no mylien
no gaps, repolarization already happening
slowest process
35
what is saltatory conduction
jumping conduction - nodes of ranvier
the myelin insulation allows the electrical field to from depolarization to jump to the next ranvier
very fast
36
The portions covered by myelin do not
experience action
potentials – they can’t, there’s no ion channels and myelin keeps ions from crossing the cell membrane
37
what are A fibres
Largest fibers, 5-20 μm, myelinated
▪ Conduct impulses at 12-130 m/sec or 280 miles/hr
▪ Large sensory nerves for touch, pressure, position, heat, cold
▪ Final common pathway for motor system
38
what are B fibres
▪ Medium fibers, 2-3 μm, non-myelinated
▪ Conduct impulses at 15 m/sec or 32 miles/hr
▪ From viscera to brain and spinal cord, autonomic efferents to
autonomic ganglia
39
what are C fibres
Smallest fibers, non-myelinated
▪ Conduct impulses at 0.5-2 m/sec or 1-4 miles/hr
▪ Impulses for pain, touch, pressure, heat, cold from skin and pain
impulses from viscera
▪ Visceral efferents to heart, smooth muscle and glands
40
what are chemical synapses?
- associated with excitable cells
The presynaptic neuron releases a neurotransmitter (NT) that
binds to receptors embedded in the post-synaptic cell membrane
▪ The “chemical” part of the chemical synapse
▪ The presynaptic terminal of the axon is the site of NT release
- crosses the synaptic cleft
The tiny distances (20 nm) from pre-synaptic to post-synaptic membrane are small enough that diffusion is an efficient transport mechanism
41
where are NT vesicles synthesized and packaged
in the rER and Golgi
and transported down the axon via microtubules (axonal transport)
42
what transports vesicles near the synaptic terminal
“molecular motor”
kinesin
43
where are neurotransmitters synthesized
cytosol of the presynaptic terminal and transported into vesicles
44
NT are transported into the vesicle using a .....Vesicles then bind to the .......and are transported to release sites
(active zone) close to the synapse
proton gradient
generated by a proton pump
actin within the presynaptic
terminal cytoskeleton
45
what are the 6 basic steps of NT release
1. AP arrives at the presynaptic terminal
2. Depolarization leads to opening of voltage-gated
calcium channels
3. Calcium enters the presynaptic terminal (as per
its Nernst potential)
4. Calcium binds to a protein associated with
neurotransmitter-filled vesicles
5. Neurotransmitter is released into the cleft as the
vesicles fuse with the presynaptic membrane
6. Neurotransmitter binds to a receptor
46
what happens at the synaptic terminal
Calcium entry is
mediated by opening
of Ca+2 VGC
▪ Not from
intracellular store
release
▪ The whole point of
the action potential
is to open Ca+2
VGC in the
presynaptic
terminal → Ca+2-induced exocytosis of NT into the
synaptic cleft
47
v-SNAREs
–a protein complex of proteins attached to vesicles
* They “force” the vesicle to fuse with the presynaptic
membrane and dock with t-SNARES
* synaptobrevin is a v-SNARE
48
t-SNARES
– a protein complex attached to the pre-synaptic
membrane → “grabs” the v-SNAREs
* Syntaxin and SNAP-25 are t-SNAREs
49
Complexin
a molecule that prevents premature release
after v-SNAREs and t-SNARES engage with each other
50
Synaptotagmin
a calcium-binding protein
* When calcium binds, it “knocks” complexin off the v-SNARE-tSNARE complex
51
Synaptotagmin and complexin prevent
premature fusion and release after zippering
52
what are the steps of vesicle release
1. v-SNARES and t-SNARES “zipper”
together
▪ Synaptotagmin and complexin prevent
premature fusion and release after
zippering
2. AP → depolarization → Ca+2 VGC
opening → calcium influx into the presynaptic terminal
3. Calcium binds to synaptotagmin →
disengagement of complexin
4. The synaptic vesicle fuses when
complexin disengages → release of NT
into the synapse
5. The v-SNAREs and t-SNARES disengage,
and the vesicle is re-used
▪ This occurs after intracellular calcium levels
decrease
53
what does the toxin produced by Clostridium botulinum do?
They impair the assembly and function of v-SNAREs
and t-SNARES
* This impairs fusion of vesicles with the presynaptic
membrane
54
botox prevents ....
Prevents release of acetylcholine from motor neuron pre-synaptic terminals, which is necessary to excite contraction in skeletal muscle
55
botox A binds to
SNAP-25, a v-SNARE
56
acetylcholinesterase
degrades acetylcholine to
acetate and choline
▪ Reabsorbed by nearby
astrocytes
- Reabsorbed by the presynaptic terminal
▪ Diffuse out of the cleft and
carried away by blood
57
Some NTs cause anion channels to open, which results in
a graded hyperpolarization
58
Some NTs cause cation channels to open, which results in:
Depolarization for sodium and (to a lesser extent) calcium
* Hyperpolarization for potassium
59
Many NTs cause a G-protein or other intracellular cascade of
second messengers which can ...
These can open or close channels for longer periods,
change kinase activity, even change gene expression
60
Ionotropic receptors open an ion channel when
they bind to their ...
ligand
61
NMDA receptor – binds the NT glutamate to ....
sodium and
calcium channel opening
62
Nicotinic acetylcholine receptor – binds to acetylcholine causing
sodium channel opens
63
GABA(a) and glycine receptors
bind to GABA and
glycine respectively → Cl- channel opens
64
metabotropic receptors are linked to
G protein signalling
65
Ach excite receptor and signal
Nicotinic
M1, M3, M5
→ Ionotropic, sodium channel
→ increases in calcium (metabotropic)
66
Ach inhibit receptor and signal
M2, M4
→ Decrease in calcium or cAMP or opens a Gprotein-gated K+ channel (metabotropic)
67
GABA – inhibit receptor and signal
GABAa
→ Ionotropic, Chloride channel
68
Glutamate - excite receptor and signal
NMDA, AMPA
→ Ionotropic sodium + calcium channels
69
Glycine – inhibit receptor and signal
Strychnine-sensitive
→ Ionotropic, Chloride channel
70
Norepi. - excite receptor or signal
Alpha-1
Beta-1
→ Increased IP3 and calcium (metabotropic)
→ Increased cAMP (metabotropic)
71
what are three important forms of Ach receptor
Nicotinic – the NT of the neuromuscular junction, also widely expressed throughout the brain
▪ Excitatory muscarinic – important for cognitive function, memory
▪ Excitatory and inhibitory muscarinic are key for the activity of the
autonomic nervous system
72
most important inhibitory NT of the “intracranial” CNS
GABA
73
most important inhibitory NT of the spinal cord
Glycine
74
most common excitatory NT of the CNS - NMDA receptors are very important for learning and memory
* Glutamate
75
autonomic nervous system functions, also cortical and
limbic system roles
Norepinephrine
76
So a neurotransmitter binds to an ionotropic receptor – what’s next?
inhibitory receptor, that results in dendrite
hyperpolarization
excitatory receptor, that results in dendrite
depolarization (
77
Activation of ionotropic receptors bring about
graded potentials in the dendrites and cell body
78
A graded potential is
any change in membrane potential that doesn’t result in an action potential
79
what are the properties of graded potential (4)
- They get smaller (decremental) over time and the further
they travel along the cell membrane
▪ They can vary in magnitude
▪ They can “add together”, or summate
▪ They can be excitatory (depolarization) or inhibitory
(hyperpolarization)
* Excitatory = excitatory post-synaptic potential (EPSP)
* Inhibitory = inhibitory post-synaptic potential (IPSP)
80
Even if an EPSP is higher than threshold, no
AP will occur unless
Na+ VGC are present
81
what lasts longer, graded or action potentials?
graded
82
EPSP
excitatory post synaptic potential
83
IPSP
inhibitory post synaptic potential
- inhibitory receptor activated = hyper polarization
84
what is spacial summation
If multiple EPSPs from
different sites (say
points 1 and 2) meet at
the same time, same
place on the membrane
85
what is temporal summation
If multiple graded potentials add up in a “staircase” fashion over time
86
Many different axons synapsing on one neuron can result in a wide array of
EPSPs and IPSPs
87
EPSPs and IPSPs can be :
long- or short-lasting, depending on
the receptor and how many action potentials are being sent per second
88
The net result – all of these EPSPs and IPSPs can be integrated at
the axon hillock
89
Chemical synapses and graded potentials add an extra level of
complexity
90
Metabotropic receptors can have very long-lasting effects that include
protein synthesis and long-lasting intracellular signals
91
contrast graded potentials to action potentials
Arise mainly in dendrites and cell body vs Arise at trigger zones and propagate along the axon
Ligand-gated or mechanically gated ion
channels vs Voltage-gated channels for Na+ and K+
Decremental; permit communication over
short distances, degrade over long distances vs Propagate and thus permit communication
over longer distances
Depending on strength of stimulus, varies
from <1 mV to more than 50 mV vs All-or-none; about 100 mV
Longer, ranging from several msec to several
min vs Shorter, ranging from 0.5 to 2 msec
polarity:
May be hyperpolarizing (inhibitory to
generation of an action potential) or
depolarizing (excitatory to generation of an
action potential) vs Always consists of depolarizing phase
followed by repolarizing phase and return to
resting membrane potential
refractory period:
Not present, thus summation can occur vs Present, thus summation cannot occur
