Neuroanatomy Lecture #19: Neurotransmitters I

Front 1

Three classes of neurotransmitters

Back 1

Small molecule, neuroactive peptides and gaseous

Front 2

Small molecule Transmitters:
• 3 groups
• Place of synthesis
• Site of storage

Back 2

Small Molecule Transmitters:
• Acetylcholine, Excitatory AAs and Biogenic amines

• in the cytosol of nerve terminals
• After being taken up by empty clear vesicles, they will be tethered to the cytoskeleton until release into the active zone

Front 3

Filling a synaptic membrane depends on this

Back 3

An established H+ gradient across the vesicular membrane

Typically, An (H+)-ATPase pumps H+ into the cell while an antiport shuttles an H+ out of the cell in exchange for a desired NT

Front 4

Briefly describe what accounts for the rapid rising phase (1) and slow falling phase of intracellular [Ca2+]

Back 4

Rising phase: attributed to the AP. The Ca2+ influx is needed for exocytosis

Falling phase: membrane channels are either pumping out Ca2+ or sequestering it from the cytosol

On the plasma membrane of the terminal nerve ending are a (Ca2+)-ATPase and a Ca2+/Na+ exchanger

In the cytosol is the Sarcoplasmic reticulum which sequester Ca2+ using SER-Ca2+ ATPase.

Front 5

Exocytosis of of NTs:
• Role of Synapsin
• What causes Synapsin to be Phosphorylated?
• Role of Rab proteins
• Which proteins are involved in docking of the vesicle to the plasma membrane? (4)
• Which protein helps the vesicle fuse with the nerve terminal membrane?
• What is needed for the vesicle to fuse with the membrane?

Back 5

Exocytosis of of NTs:
• To tether the vesicle to the cytoskeleton

• Rising [Ca2+]i

• brings the vesicles to the active zone for exocytosis

• Two t-SNARE and Two v-SNARE proteins are needed. The t-Snare proteins, which are located on the plasma membrane, are Syntaxin and Synaptobrevin. They bind, respectively, to two v-SNARE proteins, Synaptobrevin and Synaptotagmin.

• Synaptophysin
• A local rise in [Ca2+]i at the active zone

Front 6

This determines the release of small molecule NTs vs that of small molecule NTs AND neuropeptides

Back 6

Small molecule NTs are stored in small clear vesicles while Neuropeptides are stored in large dense core vesicles.

What determines their release are stimulation rates:
- Low nerve stimulation rates (< 10Hz) small clear vesicles are preferentially released

- High nerve stimulation rates (>100Hz) induces both small and large core vesicles to be released

Remember that the stiulation rates are dependent on the level of [Ca2+]i

Front 7

Vesicular Membrane Recycling:
• General process by which vesicles are recovered
• For small clear vesicles,
- this protein mediates its recycling
- once inside, it fuses with this structure

• For dense core vesicles, once they get back into the nerve terminal,
- they are transported to ....... via this process
- the above process is driven by which protein?
- the vesicles are filled with.......

Back 7

Vesicular Membrane Recycling:
• General process by which vesicles are recovered
• For small clear vesicles,
- clathrin
- endosome

• For dense core vesicles, once they get back into the nerve terminal,
- ... to the soma via retrograde transport
- dynein
- ... filled with propeptides

Front 8

Miniature end plate potentials:
• The means by which they were induced
• Their existence showed this

Back 8

minEPPs
• They were not induced, but were spontaneously generated in the ansence of nerve stimulation
• Their existence showed that the nerve terminal is releasing ACh spontaneously

Front 9

What did replacing Ca2+ with Mg2+ do to EPPs? (2)

Back 9

• It lowered the probability of a vesicle being released via exocytosis
• It lowered the value of EPPs, showing quantal fluctuations as all EPPs are multiples of minEPPs

Front 10

Def of Quantal size

Back 10

The number of transmitter molecules in a vesicle

Front 11

Def of Quantum Content

Back 11

The number of Quanta released by a single impulse

Front 12

Botulinum toxin:
• Its mechanism of action
• What it prevents
• A clinical use

Back 12

Botulinum toxin:
• It is a protease that degrades synaptobrevin, preventing the vesicle from docking
• It irreversibly prevents ACh release
• Tx of dystonia, irreg clonic contractions of muscle

Front 13

Tetanus Toxin:
• Its target cell
• Its mechanism of action
• What it prevents

Back 13

Tetanus Toxin:
• Glycinergic interneurons
• It is a protease that degrades synaptobrevin
• It prevents vesicular release of glycine irreversibly

Front 14

α-Latrotoxin:
• Type of molecule
• Its mode of action
• The result of its actions

Back 14

α-Latrotoxin:
• peptide
• It binds to the neurexin/synaptotagmin promoting fusion of cholinergic vesicles
• After the large release of vesicular ACh, the temrminal becomes depleted of vesicles leading to spasms and succeeding flaccid paralysis

Front 15

Aminoglycoside Antibiotics:
• two examples
• mode of action
• How the effects of the Abs can be reversed
• What they do at the NMJ at high concentrations

Back 15

Aminoglycoside Antibiotics:
• Neomycin and Streptomycin
• inhibit exocytosis at the nerve terminal
• Their effects are reversed competitively by raising [Ca2+] levels
• They can block nAChR at high concentrations

Front 16

4-Aminopyridine:
• Mode of action (2)
• The probability of this is increased

Back 16

4-Aminopyridine:

• It blocks K+ channels, prolonging the duration of an impulse (preventing re-polarization) and enhancing Ca2+ into the motor nerve ending

• The probability of ACh release is increased (Quantum Content is increased)

Front 17

These kinds of synapses can lead to neurotransmitters altering Quantal release

Back 17

Axo-axonic synapses; the transmitters released from the pre-synaptic cell bind to the receptors on the axon of the post-synaptic cell, inhibiting/reducing the release of its NTs

Front 18

Hypocalcemia:
• a disease that causes it
• Three consequences of it

Back 18

Hypocalcemia:
• Hypoparathyroidism
• Three consequences
1) The lack of Ca2+ in the ECF lowers the membrane potential gradient btwn the inside and outside of the cell, lowering the threshold for excitability, making it more likely to spontaneously depolarize

2) Lower Ca2+ makes the plasma membrane more permeable to ions and small solutes, also leading to depolarization

3) However, the lack of Ca2+ will also lead to less transmitter/quanta released from the pre-synaptic terminal

Front 19

β-bungarotoxin
• what it binds to
• the end result

Back 19

β-bungarotoxin
• binds to actin irreversibly
• Blocks ACh release