Neurophysiology L4: Synaptic Neurotransmission Flashcards

1
Q

What is an electrical transmission?

A

When an action potential gets to a terminal, it has to transmit the electrical signal across the cell

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2
Q

What are 3 features of electrical transmission?

A
  1. Gap junctions allow direct electrical coupling between neurons.
  2. Generally rare in neurons.
  3. Common in cardiac and smooth muscle
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3
Q

Gap junctions allow direct __________ between neurons. ______ transmission is the main way of neurons communicating with each other or muscles

A

electrical coupling; chemical

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4
Q

Electrical transmission is generally rare in ______.

A

neurons

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5
Q

Main way of transmission in cardiac and smooth muscle is ______ transmission.

A

Electrical

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6
Q

Why is electrical transmission advantageous in cardiac muscle?

A

Advantageous in cardiac muscle because you want contraction in unison.- No stimulation happens. Electrical signals is generated at the SA node. Whole signal is transmitted very quickly to the rest of the cardiac muscle and and the whole cardiac muscle contracts in a unison. Mainly caused by electrical signals travelling from one cell to the other - coupled together.

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7
Q

How does electrical transmission work in smooth muscle?

A

In blood vessels (only in arterial smooth muscle) Only the surface of the smooth muscles are innervated by varicosities (nerve endings), deeper smooth muscles cells are not innervated. An electrical signal is generated on the surface and the signal is transmitted through the smooth muscles (because they’re coupled together) and the blood vessel constricts to reduce or increase the blood flow in a particular bed.

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8
Q

A pool of motor neurons (particular muscle) _____ (are/aren’t) coupled together. When stimulated –> _______ (all/none) stimulated –> muscle contracts (uniform way) - useless if controlled movement.

A

are; all

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9
Q

You loose that communication between _______ neurons in development, but they still work together and contract in ______ (not at the spinal cord level, but at the brain). The pattern is established on the _____ of the brain.

A

motor; unison; motor cortex

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10
Q

What are electrical synapses in relation to synaptic transmission?

A

Originally thought by some to be the main type of connection between “excitable” cells such as neurons

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11
Q

What are chemical synapses in relation to synaptic transmission?

A
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12
Q

What is a synaptic cleft?

A
  • Synaptic clef/gap - neurons don’t make contact with each other.
  • Contains recognition molecules - tells nerve terminal that they’re close to a muscle and tells the muscle that there’s a nerve terminal close by - communicating with each other.
  • Occurs early in development.
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13
Q

What is a synaptic vesicle?

A
  • Cannot move around freely - the nerve terminal is filled with other things.
  • Vesicular associated proteins push them towards the release point.
  • They are pulled towards the central part (active zone - where transmission actually happens).
  • They are primed - conditioned so that they’re ready to go when an action potential comes down - very close to being released.
  • All it takes is a little bit of calcium to come in when an action potential comes down and the vesicle releases its contents.
  • These proteins and filaments inside the neuron are bringing the vesicles to the appropriate place, where they’re going to be released effectively and quickly. This is why synaptic transmission is very fast.
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14
Q

What are voltage gated Na2+ channels?

A
  • Calcium channels can also be blocked.
  • Animals living in cone shell has a barb containing conotoxins.
  • Conotoxins block calcium channels very effectively -> block neurotransmission -> you die very quickly.
  • Omega-conotoxin - used as pain killer.
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15
Q

What is a transmitter-gated channel?

A
  • Post synaptic receptors are highly concentrated in this area - 10,000 times more concentrated than elsewhere.
  • This is so that when the transmitter comes out, the first (second) thing that it sees is the receptors and hits it.
  • The receptors open up, allowing sodium to flow in - local depolarization.
  • The first thing that the transmitter sees is a hostile environment - acetylcholinesterase is found all over the place (enzyme that breaks down acetyle choline). As soon as acetyle choline comes out at the neuromuscular junction, the first round of acetyle choline will never see the receptors - gets broken down by the enzyme and occupies it. The remainder of acetyle choline passes through and hits the receptors -> receptors open and local depolarization happens. Then the acetyle choline comes off and immediately, acetylecholinestrase breaks that down -> Terminal goes back to a ready state again and receptors reactivate themselves, getting ready for a second stimulus.
  • If acetyle choline is not broken down fast enough, you get a depolarising block. They block acetylecholinestrase -> you get excessive amount of acetyle choline hitting receptors -> receptors become inactivated -> you become paralysed -> your lungs stop working -> death
  • The system is very well balanced - it relies on acetyle choline, cholinesterase, amount of transmitter, amount of receptors being in balance
  • Any imbalance will cause a disease.
  • Some diseases are known to affect this.
    • E.g. Myasthenia gravis - immune system attacks acetyle choline receptors -> end up with weakness in contractions.
    • E.g. Multiple sclerosis - immune system attacks myelin sheaths -> signals become more confused -> slower signals -> paralysis.
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16
Q

Post synaptic receptors are ______ (highly/lowly) concentrated in this area - 10,000 times more concentrated than elsewhere. Why?

A

highly

  • This is so that when the transmitter comes out, the first (second) thing that it sees is the receptors and hits it.
  • The receptors open up, allowing sodium to flow in - local depolarization.
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17
Q

The first thing that the transmitter sees is a _____ environment - acetylcholinesterase is found all over the place (enzyme that breaks down acetylcholine). As soon as acetylcholine comes out at the _______, the first round of acetyle choline will never see the receptors - gets broken down by the enzyme and occupies it. The remainder of acetylcholine passes through and hits the receptors -> receptors open and local ______ happens. Then the acetylcholine comes off and immediately, acetylecholinestrase breaks that down -> Terminal goes back to a ready state again and receptors ______ themselves, getting ready for a second stimulus.

A

hostile; neuromuscular junction; depolarization; reactivate

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18
Q

If acetylcholine is not broken down fast enough, you get a _____ block. They block acetylecholinestrase -> you get ____ amount of acetylcholine hitting receptors -> receptors become _______ -> you become _____ -> your lungs stop working -> death

A

depolarising; excessive; inactivated; paralysed

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19
Q

Any imbalance of ______, _______, ______ and ______ will cause a disease.

A

acetyle choline, cholinesterase, amount of transmitter, amount of receptors

20
Q

What are 2 examples of diseases caused by imbalance in system? What is the treatment?

A
  • E.g. Myasthenia gravis - immune system attacks acetyle choline receptors -> end up with weakness in contractions.
  • E.g. Multiple sclerosis - immune system attacks myelin sheaths -> signals become more confused -> slower signals -> paralysis.
  • Treatment for these diseases are to suppress the immune system.
21
Q

What are 7 steps of chemical transmission?

A
  1. AP into presynaptic nerve terminal
  2. Activation of voltage gated calcium channels(VGCCs) and Ca++ influx; Large calcium concentration difference outside to inside.
  3. Synaptic vesicles fuse with presynaptic membrane and release their content into the synaptic cleft; Involves vesicular associated proteins
  4. The neurotransmitter diffuses to postsynaptic membrane.
  5. Activation of neurotransmitter-gated ion channels.
  6. Ions travel through channels may cause depol. or hyperpolarisation; depending on what channels are open - sodium depol. in CNS, chloride channels (activated by GABA) hyperpol. - inhibition
  7. Transmitter is removed after very short period. Three mechanisms:
  • Broken down by enzymes. (eg. acetylcholinesterase)
  • Diffuse away and broken down elsewhere.
  • Re uptake into presynaptic terminal or glial cells.
22
Q

Chemical transmission: Step 1

A

AP into presynaptic nerve terminal

23
Q

Chemical transmission: Step 2 (after AP in presynaptic nerve terminal)

A
  • Activation of voltage gated calcium channels(VGCCs) and Ca++ influx
  • Large calcium concentration difference outside to inside.
24
Q

Chemical transmission: Step 3 (after activation of voltage gated channels)

A
  • Synaptic vesicles fuse with presynaptic membrane and release their content into the synaptic cleft.
  • Involves vesicular associated proteins
25
Q

Chemical transmission: Step 4 (after release of content into synaptic cleft)

A

The neurotransmitter diffuses to postsynapticmembrane.

26
Q

Chemical transmission: Step 5 (after diffusion of post synaptic membrane)

A

Activation of neurotransmitter-gated ion channels.

27
Q

Chemical transmission: Step 6 (after activation of neurotransmitter-gated ion channels)

A
  • Ions travel through channels may cause depol. or hyperpolarisation.
  • depending on what channels are open - sodium depol. in CNS, chloride channels (activated by GABA) hyperpol. - inhibition
28
Q

Chemical transmission: Step 7 (after ions have travelled through channels to cause depolarisation or hyperpolarisation)

A

Transmitter is removed after very short period.

Three mechanisms:

  • Broken down by enzymes. (eg. acetylcholinesterase)
  • Diffuse away and broken down elsewhere.
  • Re uptake into presynaptic terminal or glial cells.
29
Q

What is fast synaptic transmission?

A
  • Mediated by ligand-gated ion channels.
  • Fast excitatory NTs –> Ach and glutamate {both activate channelsequally permeable to Na+ and K+}
  • When these channels open the cell depolarize –> AP.
30
Q

Describe- Fast synaptic transmission: Driving force into channel = Ex-Vm

A

A:

Chemical gradient (higher concentration of sodium on the outside) and electrical gradient (-ve ions inside attract +ve ions) both drives sodium ions in. Therefore, as soon as a receptor (acetyle choline) opens, sodium is going to come in.

B:

Chemical gradient: high concentration of potassium inside, lower concentration of potassium outside - potassium wants to move out. But electrical gradient: positive on outside, negative on inside - potassium wants to stay inside. The only thing that’s driving potassium out is the concentration gradient.

31
Q

Describe- Fast synaptic transmission: At -90mV (at Vm = EK)

A

Strong Na+ influx (ENa-Vm) =70 + 90 = 160mV K+ -no net movement of ions as Vm=EK

A:

Therefore, when an acetyle choline receptor opens, most of the depolaristion will be due to sodium rushing in (local potential). Potassium doesn’t do much - opposite electrical gradient to chemical gradient - stays in.

32
Q

Describe- Fast synaptic transmission: At -70mV

A

Strong Na+ influx (ENa-Vm) 140mV

A:

Until, enough sodium has come in to change the electrical gradient, then potassium will want to go out as inside is now positive.

33
Q

Why does fast synaptic transmission occur?

A

when a channel opens, the main thing that happens is the depolarisation driven by the sodium coming in. But as the sodium (depolarisation) increases inside, the current flow of sodium going in starts to decrease - imbalance of chemical and electrical gradient is becoming smaller and smaller.

34
Q

What are excitatory synapses?

A
  • cell depolarises
  • “excitatory post-synaptic potential” (EPSP)
    • Glutamate- main excitatory transmitter (brain)
  • initiates AP
35
Q

What are inhibitory synapses?

A
  • cell hyperpolarises
  • “inhibitory post-synaptic potential” (IPSP)
  • either it prevents cell from reaching AP threshold or stops AP from propagating Na
    • Makes the cell less excitable
    • Inside goes negative, threshold remains steady (RMP You need more excitatory transmitter to overcome the bigger gap between RMP and threshold potential.
    • How we sleep. GABA acting on thalamus is inhibiting sensory information coming in by making neurons less excitable. Unless something unusual happens that you didn’t expect –> excitation overcomes and reaches the threshold potential –> you wake up.
36
Q

What are chemical synapses in regards to synaptic transmission?

A
  1. AP opens voltage-gated Ca2+ channels
  2. Ca2+ enters and triggers exocytosis of transmitter from vesicles
  3. Transmitter inactivated by one or more:
    • Enzyme in synapse
    • Re-uptake by releasing neurons
    • Diffusion from synapse
37
Q

What are the 2 different types of Acetylcholine (ACh)?

A
  1. “Nicotinic” receptor
  2. “Muscarinic” receptor
38
Q

What is the “Nicotinic” receptor of Acetylcholine (ACh)?

A

e.g. skeletal muscle cells

  • directly gated channel
  • When ACh hits the receptors, they open up and sodium comes in
  • opened by ACh binding
  • permeable to Na+ and K+
  • main effect is Na+ influx
  • fast EPSP results
39
Q

What is the “Muscarinic” receptor of Acetylcholine (ACh)?

A

Eg. smooth muscle cells (eg. gut)

  • indirectly gated channels
  • closed by ACh binding
  • permeable decreased to K+
    • If potassium channels are blocked, there’s no potassium moving in or out of the cell, the cell moves towards 0 potential - because potassium moving out of the cell causes cell to be negative (-70mV). Cell slowly depolarises to 0 -> slow EPSP -> slow contraction
  • slow EPSP result
40
Q

What are 6 common neurotransmitters?

A
  1. Acetylcholine
  2. Noradrenaline
  3. Adrenaline
  4. Serotonin
  5. GABA
  6. Glutamate
41
Q

What are 6 common neurotransmitters?

A
  1. Acetylcholine
  2. Noradrenaline
  3. Adrenaline
  4. Serotonin
  5. GABA
  6. Glutamate
42
Q

What is Acetylcholine?

A
  • some CNS neurons
  • all autonomic pre-ganglionic neurons
  • all parasympathetic post-ganglionic neurons
43
Q

What is noradrenaline?

A
  • some CNS neurons
  • all sympathetic post-ganglionic neurons
  • adrenal medulla secretory cells
44
Q

What is adrenaline?

A
  • fight or flight response
  • some CNS neurons
  • adrenal medulla secretory cells
45
Q

What is serotonin?

A
  • some CNS neurons
46
Q

What is GABA?

A
  • many CNS neurons (inhibitory)
47
Q

What is Glutamate?

A
  • many CNS neurons (excitatory)