Excitable cells (lectures 8-13) Flashcards

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1
Q

What are the 4 regions of a neurone?

A

Cell body
Dendrites
Axon
Axon terminal

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2
Q

What is an action potential?

A

A rapid change in membrane potential

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3
Q

What does the unequal distribution of ions across the membrane do?

A

Leads to a slight negative charge inside the membrane
Chemical disequilibrium
Resting membrane potential (RMP)

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4
Q

How is the RMP maintained?

A

The high permeability of the membrane to K+
The active transport of Na+ across the membrane

Both via transmembrane proteins

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5
Q

What are K+ leaky channels?

A

Allow K+ to flow out of the cell down its conc gradient

Ion channel mediated facilitated diffusion

Inside of cell becomes more negative and outside becomes more positive

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6
Q

What are Na+/K+ ATPases?

A

3 Na+ out and 2 K+ in

Na+ wants to flow down its conc gradient into the cell but can’t as its pumped out by active transport

Pump is electrogenic not electroneutral

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7
Q

What is the equilibrium potential (Ek) ?

A

The voltage when K+ stops moving

When the electrical gradient is equal and opposite to the conc gradient

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8
Q

What is the Nernst equation?

A

Determines the equilibrium potential

Eion = (-RT / zF) x ln( [ion-in] / [ion-out] )
R = gas constant 
T = absolute temp 
z = valence 
F = Faraday constant
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9
Q

How can you get the RMP?

A

All potentials generated by diffusion gradients sum to give the RMP of the membrane

Biggest weighting given to the most permeable (K+)

Rapid witch in permeability from K+ to Na+ causes the AP

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10
Q

What is the order of an AP?

A

Resting
Depolarisation
Repolarisation
Hyperpolarisation

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11
Q

What are voltage gated ion channels?

A

Activated by voltage change
Allows ionic currents to cross the membrane

Vg Na+ channels - Na+ enters down conc gradient
Vg K+ channels - K+ leave down conc gradient

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12
Q

What happens in resting state?

A

High K+ inside
High Na+ outside
All channels closed

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13
Q

What happens when the neurone becomes stimulated?

A

Some vg Na+ channels open
Na+ flows in
ATP pump tries to remove them but can’t keep up
Membrane potential begins to rise

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14
Q

What happens when threshold membrane potential voltage is reached?

A

All vg Na+ channels open
Huge influx of Na+ into cell
Sharp rise in membrane potential
At the end some vg K+ channels begin to open

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15
Q

What happens during early repolarisation?

A
All vg Na+ channels become inactivated 
Na+ can not longer enter cell 
All vg K+ channels open 
Cell becomes more negative 
Membrane potential repolarises
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16
Q

What happens during hyperpolarisation?

A

Some vg K+ channels still open
Na+ channels blocked
Vg K+ channels slower to activate and turn off
Na+/K+ ATP pump returns to RMP

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17
Q

What does gNa+ and gK+ mean?

A

Sodium and potassium conductance

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18
Q

At what voltage are vg Na+ channels activated?

A

-55 mV

Vg Na+ channels open rapidly
Na+ rushes into cell through ‘activation’ gate of the channel

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19
Q

Whats the difference between activation gates and deactivation gates?

A

Activation gates = voltage dependant

Deactivation gates = time dependent

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20
Q

What is the absolute refractory period?

A

The period in which the membrane cannot generate another AP no matter how big the stimulus

Na+ channels are inactivated

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21
Q

What is the relative refractory period?

A

The period in which the membrane can generate another AP but only if the stimulus is bigger than normal

Some Na+ channels are recovered
Some K+ channels still open

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22
Q

Where does an AP start?

A

At the axon hillock
Where the axon leaves the cell body

If the sum of current signals reaches threshold at the hillock then AP starts

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23
Q

How do AP travel?

A

By current loops

AP depolarisation activates vg Na+ channels further along
Depolarises neighbouring region

Refractory period stops propagation backwards

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24
Q

What affects the velocity of an AP?

A
Diameter (D)
Membrane resistance (Rm)

To increase velocity:
• Increase D
• Increase Rm - via myelination

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25
Q

What is myelination?

A

Closely packed layers of Scwann cells form myelin sheath
Insulates the plasma membrane of the axon
Isn’t continuous due to Nodes of Ranvier

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26
Q

What are nodes of Ranvier?

A

Breaks in the myelin sheath
Occur every 1-2mm
Current jumps from node to node
= saltatory conduction

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27
Q

What happens when neurones become unmyelinated?

A

Multiple Sclerosis
Most common neurodegenerative disorder

Results in AP being unable to jump from node to node
Is scattered and progressive
Gradual loss of motor control

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28
Q

What happens at a neuromuscular junction?

A

1) AP depolarises presynaptic membrane
2) Causes opening of vg Ca++ channels
3) Ca++ rushes in causing vesicles to fuse with the presynaptic membrane
4) Vesicles release Ach into synaptic cleft by exocytosis
5) Ach diffuses across cleft and binds to receptors on postsynaptic membrane (muscle endplate)
6) Causes ligand-gated Na+ channels to open
7) Na+ rushes in and K+ rushes out of the muscle endplate
8) Endplate potential (EPP) reaches -15mV

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29
Q

Why are there no APs at the junctional folds of the muscle endplate?

A

There are no vg Na+ channels

EPPs in the junctional folds trigger APs nearby where there are vg Na+ channels
These APs propagate deep within the muscle to activate contraction

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30
Q

What is the smallest EPP that can be generated?

A

The mini EPP - same shape as the EPP but smaller and occurs at random at rest

Mini EPP always the same size

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31
Q

How are Ach molecules recycled?

A

By acetylcholinesterase

Breaks it down into choline and acetate

32
Q

What is skeletal muscle made of?

A

Muscle fibres
One cell with many nuclei
Each fibre contains many myofibrils

33
Q

What makes up the sarcomere?

A
A band 
M line 
I band 
Z line 
H zone
34
Q

what happens during contraction?

A

muscle shortens considerably
thin filaments slide over the thick filaments

A band stays the same
I band decreases
H zone decreases
distance between Z lines decreases

35
Q

thick filament

A

made of myosin - formed of a long tail and a head
100s of myosins make up each filament
M line holds thick filament together

36
Q

thin filament

A

made of actin, tropomyosin and troponin
G-actin molecules form F-actin strands
2 F-actin strands wind together in a double helix

long filaments of tropomyosin wind around the F-actin double helix

troponin molecules bind to actin and tropomyosin

37
Q

troponin structure

A

has 3 subunits

T and I subunits bind to tropomyosin and actin, blocking the myosin binding site

Ca++ binds to C subunit to uncover the myosin binding site

38
Q

what are T tubles?

A

invaginations of the muscle membrane (sarcolemma) penetrating deep into the muscle fibre

39
Q

what is the sarcoplasmic reticulum?

A

a tubular structure that surrounds the myofibrils, enlarging into terminal cistern (TC) near the T tubles

stores lots of Ca++

40
Q

what do the T tubles do?

A

get the AP into parts of the muscle that other membranes cannot reach

AP in the t-tubles triggers Ca++ release from the TC of the SR

rise in intracellular Ca++ conc in the muscle causes contraction

41
Q

what happens in excitation-contraction coupling?

A

1) Ca++ binds to troponin C, uncovering the myosin binding site on the actin molecule - cross bridge formation
2) myosin is in its high energy state having hydrolysed ATP to ADP + P
3) myosin heads rotate, pulling the thin filament towards the centre of the sarcomere - power stroke
4) ATP binds to myosin head, breaking the actin-myosin bond releasing ADP + P
5) ATP is split returning myosin to its high energy state

42
Q

what causes relation of excitation-contraction coupling?

A

removal of Ca++ by the SR

ATP binding to myosin

43
Q

what 2 categories is the human nervous system split into?

A

CNS

PNS

44
Q

what makes up the CNS?

A

brain

spinal cord

45
Q

what makes up the PNS?

A

peripheral nerves

everything else

46
Q

function of the CNS

A

integrate all the incoming information and decide what action is needed

interneurones

47
Q

function of the PNS

A

responsible for sensory inputs and motor outputs

sensory neurones
motor neurones

48
Q

what is the motor neurone?

A

efferent neurone

multipolar - many processes emanate from the cell body

49
Q

what is the interneurone?

A

very large dendritic tree
lots of integration of synaptic signals from sensory receptors

multipolar - many processes emanate from the cell body

50
Q

what is the sensory neurone?

A

afferent neurone
2 different types

for smell and vision:
• cell body in the middle
• bipolar - 2 processes emirate from cell body
• unmyelinated

all others have an offset cell body
pseudo unipolar - axon splits into 2 branches: one branch runs to the periphery and the other to the spinal cord

51
Q

what intracellular makeup do all neurones have?

A
peptides synthesised and packaged 
fast axonal transport 
vesicle contents released by exocytosis 
synaptic fescue recycling 
retrograde fast axonal transport 
old membrane components digested in lysosomes
52
Q

what are special characteristics of all neurones?

A

dont divide - foetal neurones lose their ability to undergo mitosis

longevity - can live and function for a lifetime

high metabolic rate - require abundant O2 and glucose

53
Q

what are the 2 types of electrical signals in neurones?

A

action potentials

graded potentials

54
Q

what are action potentials?

A

large, uniform depolarisations that travel rapidly for long distances without loosing strength

all or none response

55
Q

what are graded potentials?

A

variable strength signals that travel over short distances and lose strength

56
Q

where do graded potentials occur?

A

occur in dendrites, cell bodies or axon terminals

anywhere that isn’t the axon

57
Q

why is it called a graded potential?

A

size/amplitude is directly proportional to the strength of the triggering event

large stimulus = strong graded response
small stimulus = weak graded potential

58
Q

what is a depolarising graded potential?

A

excitatory postsynaptic potential (EPSP)

e.g. Na+ entering the cell

59
Q

what is a hyperpolarising graded potential?

A

inhibitory postsynaptic potential (IPSP)

eg. Cl- entering the cell or K+ leaving the cell

60
Q

what happens to graded potentials when they reach the axon hillock?

A

if graded potentials reaching the axon hillock depolarise the membrane to the threshold voltage (-55mV), an AP is initiated

61
Q

what is a subthreshold EPSP?

A

failing to reach the threshold

graded potential in cell body is above threshold
diminished in amplitude as it travels through the cell body
when reaches the axon hillock it is below threshold when reaches the trigger zone
no AP fired

62
Q

what is a suprathreshold EPSP?

A

stronger graded potential
diminishes in size but still above threshold when it reaches the trigger zone
AP is fired

63
Q

what does the frequency of APs show?

A

the strength or duration of the stimulus

stronger the stimulus, the higher the frequency of APs

64
Q

what is divergence?

A

presynaptic neurone branches to affect a large number of postsyntapic neurones

branches are called collaterals - collateral axons

65
Q

what is convergence?

A

a large number of presynaptic neurones converge to affect a smaller number of postsynaptic neurones

multiple inputs can influence the outputs off a single postsynaptic cell

66
Q

what is spacial summation?

A

EPSPs originate simultaneously at different locations on the neurone

3 excitatory neurones fire and all their EPSPs separately are subthreshold
subthreshold EPSPs arrive at the trigger zone together and sum to create a supratheshold signal
AP is generated

67
Q

what is postsynaptic inhibition?

A

when EPSPs are diminished by IPSPs

no AP generated

68
Q

what is temporal summation?

A

summing that occurs from graded potentials overlapping in time

69
Q

what is postsynaptic integration?

A

incorporates both spacial and temporary summation

70
Q

what is presynaptic modulation?

A

neurones terminate on or close to the presynaptic axon terminals

can be excitatory or inhibitory
provides a more precise means of control than postsynaptic modulation

71
Q

what are the 2 mechanisms that neurotransmitter receptors work by

A

ligand gated ion channels - inotropic receptors

GPCR - metabotropic receptors

72
Q

what are inotropic receptors?

A

nicotinic receptors

fast

73
Q

what are metabotropic receptors?

A

muscarinic receptors

slow

74
Q

what is long term potentiation (LTP)?

A

process by which repetitive stimulation at a synapse increases the efficacy of transmission at that synapse

molecular basis of learning and memory
can persist for days or weeks

glutamate is the main excitatory transmitter in the CNS

75
Q

How does LTP work?

A

1) glutamate is released
2) glutamate binds to 2 inotropic receptors
3) AMPA receptor is a Na+ channel so triggers an EPSP
4) repetitive stimulation results in greater depolarisation so Mg++ is ejected from the NMDA receptor
5) Ca++ flows through the NMDA receptor
6) this causes the postsynaptic cell to become more sensitive to glutamate and enhances glutamate release from the presynaptic cell

76
Q

what is synaptic plasticity?

A

LTP