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

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2
Q

Ohm’s law is most
useful when thinking about

A

unequal distributions of
charges very close on either
side of a membrane

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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)
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4
Q

Diffusional forces and electrical fields are very small at

A

large distances

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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
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6
Q

the electric field declines very rapidly as charges are separated by

A

distance
(ohms law)

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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

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8
Q

the ions …. to the membrane have the most effect on nernst potential

A

closest

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9
Q

At rest, neurons typically have a membrane potential that is close to the Nernst potential for

A

K+

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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
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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

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12
Q

The membrane potential is about …. in many neurons

A

-75 mV

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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

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14
Q

what is the concept of the Goldman Field equation

A

that the concentration of one electrolyte has effects on the others

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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

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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

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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
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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
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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

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20
Q

…. starts an action potential …. ends an action potenial

A

sodium
potasssium

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21
Q

… Na+ out … K+ in

A

3
2

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22
Q

K+ concentrations are …inside the axon, and ….outside

A

high
low

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23
Q

K+ is high inside the axon, therefore ..

A

it diffuses out

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24
Q

what is the resting membrane potential

A

-70mV

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25
Q

what helps to keep the resting membrane potential

A

Na/ K+ATPase pump

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26
Q

what is depolarization

A

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

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27
Q

what happens during repolarization

A
  • 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)

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28
Q

what are the two gates of action potenials

A

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)

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29
Q

The potassium voltage-gated channel does not have an inactivation gate – it opens when the cell ……., and closes once the cell is ………….

A

depolarizes

inside-negative again

It is slower to open than the sodium voltage-gated channel

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30
Q

what is the absolute refractory period

A
  • Inactivation gate of
    the Na+ VGC is
    closed
  • Another action
    potential is
    impossible until this
    gate opens
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31
Q

what is the relative refractory period

A

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

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32
Q

what are the actions of a action potential

A

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)
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33
Q

why does myelin increase conduction speed

A
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34
Q

what is continuous conduction

A

no jumping, every channel has to open, no mylien

no gaps, repolarization already happening

slowest process

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35
Q

what is saltatory conduction

A

jumping conduction - nodes of ranvier

the myelin insulation allows the electrical field to from depolarization to jump to the next ranvier

very fast

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36
Q

The portions covered by myelin do not

A

experience action
potentials – they can’t, there’s no ion channels and myelin keeps ions from crossing the cell membrane

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37
Q

what are A fibres

A

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
Q

what are B fibres

A

▪ 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
Q

what are C fibres

A

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
Q

what are chemical synapses?

A
  • 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
Q

where are NT vesicles synthesized and packaged

A

in the rER and Golgi
and transported down the axon via microtubules (axonal transport)

42
Q

what transports vesicles near the synaptic terminal

A

“molecular motor”
kinesin

43
Q

where are neurotransmitters synthesized

A

cytosol of the presynaptic terminal and transported into vesicles

44
Q

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

A

proton gradient
generated by a proton pump

actin within the presynaptic
terminal cytoskeleton

45
Q

what are the 6 basic steps of NT release

A
  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
Q

what happens at the synaptic terminal

A

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
Q

v-SNAREs

A

–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
Q

t-SNARES

A

– a protein complex attached to the pre-synaptic
membrane → “grabs” the v-SNAREs
* Syntaxin and SNAP-25 are t-SNAREs

49
Q

Complexin

A

a molecule that prevents premature release
after v-SNAREs and t-SNARES engage with each other

50
Q

Synaptotagmin

A

a calcium-binding protein
* When calcium binds, it “knocks” complexin off the v-SNARE-tSNARE complex

51
Q

Synaptotagmin and complexin prevent

A

premature fusion and release after zippering

52
Q

what are the steps of vesicle release

A
  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
Q

what does the toxin produced by Clostridium botulinum do?

A

They impair the assembly and function of v-SNAREs
and t-SNARES
* This impairs fusion of vesicles with the presynaptic
membrane

54
Q

botox prevents ….

A

Prevents release of acetylcholine from motor neuron pre-synaptic terminals, which is necessary to excite contraction in skeletal muscle

55
Q

botox A binds to

A

SNAP-25, a v-SNARE

56
Q

acetylcholinesterase
degrades acetylcholine to

A

acetate and choline

▪ Reabsorbed by nearby
astrocytes
- Reabsorbed by the presynaptic terminal
▪ Diffuse out of the cleft and
carried away by blood

57
Q

Some NTs cause anion channels to open, which results in

A

a graded hyperpolarization

58
Q

Some NTs cause cation channels to open, which results in:

A

Depolarization for sodium and (to a lesser extent) calcium
* Hyperpolarization for potassium

59
Q

Many NTs cause a G-protein or other intracellular cascade of
second messengers which can …

A

These can open or close channels for longer periods,
change kinase activity, even change gene expression

60
Q

Ionotropic receptors open an ion channel when
they bind to their …

A

ligand

61
Q

NMDA receptor – binds the NT glutamate to ….

A

sodium and
calcium channel opening

62
Q

Nicotinic acetylcholine receptor – binds to acetylcholine causing

A

sodium channel opens

63
Q

GABA(a) and glycine receptors

A

bind to GABA and
glycine respectively → Cl- channel opens

64
Q

metabotropic receptors are linked to

A

G protein signalling

65
Q

Ach excite receptor and signal

A

Nicotinic
M1, M3, M5

→ Ionotropic, sodium channel
→ increases in calcium (metabotropic)

66
Q

Ach inhibit receptor and signal

A

M2, M4

→ Decrease in calcium or cAMP or opens a Gprotein-gated K+ channel (metabotropic)

67
Q

GABA – inhibit receptor and signal

A

GABAa

→ Ionotropic, Chloride channel

68
Q

Glutamate - excite receptor and signal

A

NMDA, AMPA

→ Ionotropic sodium + calcium channels

69
Q

Glycine – inhibit receptor and signal

A

Strychnine-sensitive

→ Ionotropic, Chloride channel

70
Q

Norepi. - excite receptor or signal

A

Alpha-1
Beta-1

→ Increased IP3 and calcium (metabotropic)
→ Increased cAMP (metabotropic)

71
Q

what are three important forms of Ach receptor

A

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
Q

most important inhibitory NT of the “intracranial” CNS

A

GABA

73
Q

most important inhibitory NT of the spinal cord

A

Glycine

74
Q

most common excitatory NT of the CNS - NMDA receptors are very important for learning and memory

A
  • Glutamate
75
Q

autonomic nervous system functions, also cortical and
limbic system roles

A

Norepinephrine

76
Q

So a neurotransmitter binds to an ionotropic receptor – what’s next?

A

inhibitory receptor, that results in dendrite
hyperpolarization

excitatory receptor, that results in dendrite
depolarization (

77
Q

Activation of ionotropic receptors bring about

A

graded potentials in the dendrites and cell body

78
Q

A graded potential is

A

any change in membrane potential that doesn’t result in an action potential

79
Q

what are the properties of graded potential (4)

A
  • 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
Q

Even if an EPSP is higher than threshold, no
AP will occur unless

A

Na+ VGC are present

81
Q

what lasts longer, graded or action potentials?

A

graded

82
Q

EPSP

A

excitatory post synaptic potential

83
Q

IPSP

A

inhibitory post synaptic potential

  • inhibitory receptor activated = hyper polarization
84
Q

what is spacial summation

A

If multiple EPSPs from
different sites (say
points 1 and 2) meet at
the same time, same
place on the membrane

85
Q

what is temporal summation

A

If multiple graded potentials add up in a “staircase” fashion over time

86
Q

Many different axons synapsing on one neuron can result in a wide array of

A

EPSPs and IPSPs

87
Q

EPSPs and IPSPs can be :

A

long- or short-lasting, depending on
the receptor and how many action potentials are being sent per second

88
Q

The net result – all of these EPSPs and IPSPs can be integrated at

A

the axon hillock

89
Q

Chemical synapses and graded potentials add an extra level of

A

complexity

90
Q

Metabotropic receptors can have very long-lasting effects that include

A

protein synthesis and long-lasting intracellular signals

91
Q

contrast graded potentials to action potentials

A

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