Lecture 12: Synaptic Transmission Flashcards

1
Q

How do electrical events pass from cell to cell? = 2

A
  1. Direct electrical transmission-cardiac and some types of smooth muscle
  2. By use of a chemical mediator - chemical synaptic transmission between nerve and muscle, nerve and nerve
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2
Q

What happens during Electrical Transmission at Electrical synapse?= 4

A

1 * <5 nm between pre- and post-synaptic membrane

2 * Transmission by ion current

3 * Virtually no synaptic delay

4 * Bidirectional

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3
Q

What happens during Chemical Transmission at Chemical synapse?= 4

A

1 * 20-40 nm between pre- and post- synaptic membrane

2 * Transmission by chemical neurotransmitter

3 * Synaptic delay (at least 0.3 ms, generally 1-5 ms, can be longer)

4 * Unidirectional

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4
Q

Electrical Neurotransmission: CONNEXONS

A

Connexons – 6 identical protein subunits; allow direct electrical transmission from cell to cell (eg cardiac muscle, some smooth muscle)

Opposing conexons on pre & post-synaptic cells – directly linking cytoplasm

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5
Q

What is a JUNCTION?

A

— In neuroscience a junction is a connection from a neuron to another cell type, i.e. a synapse

— In biochemistry a junction is a type of protein that connects cells
together e.g. tight junctions and gap junctions

Can cause a bit of confusion, e.g. there are no junctions in vertebrates formed from gap junctions.

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6
Q

What is A RECEPTOR?

A

—– In neuroscience a receptor is a sensory cell that detects some
signal and turns it into an electrical potential, e.g. touch receptors.

—-In pharmacology a receptor is protein that binds a drug, hormone or neurotransmitter, e.g. nicotinic receptors

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7
Q

Steps of Chemical Neurotransmission: 5

A
  1. Action potentials DEPOLARIZE the nerve terminal
  2. Opens voltage gate calcium channels
  3. Calcium enter the nerve terminal increase local calcium concentration
  4. Vesicle contents (neurotransmitter) are released by exocytosis
  5. Neurotransmitter reacts with ligand-gated channels in post- synaptic cell membrane
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8
Q

Calcium as a Signalling Molecule: 3

A
  1. Voltage gate Nav channels are very fast
  2. Voltage gated calcium channels are slower
  3. But Ca2+ can bind and activate proteins
    - Troponin
    - Calmodulin
    -Calmodulin
    - Synaptotagmin
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9
Q

Calcium as a Signalling Molecule: TROPONIN

A

Troponin inSKELETAL MUSCLE binds Ca2+ and causes muscle contraction.

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10
Q

Calcium as a Signalling Molecule: CALMODULIN

A
  • Calmodulin in SMOOTH MUSCLE binds Ca2+ and causes muscle contraction.
  • Calmodulin in STOMACH GLAND binds Ca2+ and causes acid secretion.
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11
Q

Calcium as a Signalling Molecule: SYNAPTOTAGMIN

A

Synaptotagmin in NERVES binds Ca2+ and causes neurotransmitter release

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12
Q

UNDERSTANDING Synaptic Vesicles = 7

A
  1. Neurotransmitters are stored in VESICLES.
  2. Vesicles are stacked around the ACTIVE ZONE.
    - Active zone = release site vesicles
  3. Some vesicles are almost touching the cell membrane , DOCKED VESICLES.
  4. Voltage gated Ca2+ channels opened by action potential.
  5. Entry of Ca2+
    Vesicles fuse with pre-synaptic membrane.

6.Neurotransmitter released in distinct packages (vesicle = QUANTA)

7.**High density vesicles / high density Ca2+ channels

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13
Q

EXOCYTOSIS OF TRANSMITTER - image

A
  1. ACTIVE ZONE
  2. SYNAPTIC CLEFT
    3.VESICLE FUSION
  3. COATED PITS AND COATED VESICLES
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14
Q

Vesicle Release = procedure 5

A
  1. Readily releasable pool of vesicle (RESERVE POOL)
  2. “DOCKING” of vesicles at cell membrane; active zone
  3. A complex of SNARE (soluble NSF-attachment protein receptor) proteins docks the vesicle
  4. Binding of Ca2+ to SYNAPTOTAGMIN causes a conformational change in the SNARE complex
  5. Vesicle pulled into cell membrane producing exocytosis
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15
Q

UNDERSTANDING Vesicle Release and Recycling = 7

A
  1. VESICLES filled with neurotransmitter docked by SNARE proteins to ACTIVE ZONE
  2. An ATP dependent process is required to PRIME the vesicles for release
  3. Ca2+ entry allows calcium to bind SYNAPTOTAGMIN
  4. Triggers EXOCYTOSIS
  5. Some vesicles are restocked with neurotransmitter with out undocking, kiss-and-stay.

6.Some vesicles are undocked and refilled, kiss-and-run.

  1. Some vesicles go through ENDOCYTOSIS and reprocessed through ENDOSOMES
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16
Q

Neurotransmitter Criteria

A

“a substance that is released at a synapse by one neuron and affects another cell in a specific manner”

17
Q

Neurotransmitter Criteria = 5

A
  1. Synthesised in pre-synaptic cell and stored in PRESYNAPTIC terminal
  2. RELEASED upon STIMULATION
  3. SPECIFIC RECEPTOR must exist on post-synaptic cell
  4. Experimental application of transmitter must mimic action of NEURAL STIMULATION.

5.INHIBITING the proposed transmitter must inhibit the normal function

18
Q

Main Categories of Transmitters = 5

A
  1. simple amino acids
  2. Classical neurotransmitters
  3. Neuropeptides
  4. Purines and Pyrimidines
  5. Free radical gas
19
Q

Simple amino acids = 3

A
  • Glutamate,
  • glycine, aspartate,
  • GABA (g-aminobutyric acid, synthesised
    from glutamate)
20
Q

classical neurotransmitters = 5

A
  • ACh (acytylcholine),
  • serotonin (5-HT),

catecholamines:
- dopamine,
- adrenaline,
- noradrenaline

21
Q

neuropeptides

A

Many eg insulin, glucagon, bradykinin, hypothalamic and pituitary
hormones etc etc

22
Q

Purines and pyramidines = 3

A

ATP

ADENEINE

GUANINE

23
Q

Free Radical gas =

A

NO (nitric oxide)

24
Q

MULTIPLE RECEPTORS
(2)

A

Receptor (not just the neurotransmitter) on postsynaptic element determines postsynaptic response

  1. ACh: NICOTINIC (N-cholinergic) and MUSCARINIC (M-cholinergic) receptors
  2. NA and Adr: a and b adrenergic receptors,
    - a-adrenergic receptors contract smooth muscle,
    - b-adrenergic receptors relax smooth muscle
25
Q

Understanding Neuromuscular Junction or MOTOR END PLATE = 6

A
  1. Relatively simple
  2. Easily accessible
  3. “large”
  4. One muscle cell generally innervated by only one pre-synaptic axon (through multiple branches)
  5. Neurotransmitter directly opens one ion channel type.

6.Close relationship Ca2+ channels and synaptic active zone

26
Q

Fate of Released Neurotransmitters =

Enzymatic degradation and reuptake of acetylcholine

— 5

A
  1. Diffusion
  2. Degradation in synaptic cleft
    ——acetylcholinesterase (ACHe)
  3. REUPTAKE into pre-synaptic terminal
  4. Enzymatic destruction of reloading
  5. Involves transporter molecules
27
Q

Autoimmune Disorders = 2

A

1.Lambert-Eaton syndrome

2.Myasthenia gravis

28
Q

Lambert-Eaton syndrome = 3

A

1 * antibodies against voltage gated Ca2+ channels

2 * reduced amount of ACh released

3 * treated by decreasing ACh breakdown (eg pyridostigmine, neostigmine) or increasing calcium influx (eg 3,4-diaminopyridine)

29
Q

Myasthenia gravis = 3

A

1 * antibodies against nicotinic ACh receptors

2 * reduced number of functional receptors

3 * reversed by inhibition of acetylcholinesterase (eg pyridostigmine, neostigmine)

30
Q

Summary = 8

A
  1. A few CNS synapses are electrical, made from gap junctions like in the heart
  2. Most synapses are chemical and use a neurotransmitter
  3. The same transmitter can have different actions if the receptors
    are different
  4. Five main classes of neurotransmitter substances
  5. Depolarization of the nerve terminal opens voltage gated Ca2+ channels
  6. Calcium entry binds synaptotagmin and causes SNARE proteins to exocytose neurotransmitter
  7. Transmitters are stored in synaptic vesicles (except NO)
  8. Released transmitter is either degraded in the synaptic cleft or taken up into the pre-synaptic cells