Synaptic Transmission

Question 1

Describe what happens when the action potential reaches the axon terminal- Bhutan

Answer 1

When the action potential reaches the axon terminal voltage-dependent calcium channels which are very dense open and calcium ions move down there concentration gradient into the axon terminal! Ca 2+ conc increases.
This causes synaptic vesicles containing acetylcholine to now migrate towards the presynaptic cell membrane where they dock and fuse with the membrane and release Ach by exocytosis
Acetylcholine bind to Nicotinic ACh receptors on the postsynaptic membrane which is the skeletal muscle membrane. When the neurotransmitter binds this enables the passage of sodium into the cell and potassium out of the cell. The ions will begin to cause the polarization locally of the end plate which gives rise to a small potential- endplate potential.
If enough AC H receptors are activated and the end plate potential reaches a certain threshold successful transmission of electrical information from one side to another of the cell occurs which is transmitted through the muscle via sodium channels to cause muscle contraction

Question 2

What does the endplate potential depends on

Answer 2

It depends on the amount of acetylcholine release and the number of acetylcholine receptors activated therefore giving rise to a graded amplitude

Question 3

What happened to acetylcholine molecules after the electrical impulse is transmitted to the postsynaptic cell

Answer 3

ACh molecules disengage and unbind from the acetylcholine receptors and go back into the synaptic cleft where they are scavenged by an enzyme - acetylcholinesterase

Question 4

What does acetylcholinesterase do

Answer 4

It destroys acetylcholine molecules preventing the rebinding endless of times on the acetylcholine receptors- it’s a hydrolyzes acetylcholine into two component parts acetate and Choline

Question 5

What happens to acetate

Answer 5

It diffusers away and it’s not retained at the synapse

Question 6

What happens to Choline

Answer 6

It is retained for further use by another structure on the presynaptic terminal membrane- Choline uptake carrier
This uses the NA+ concentration gradient to drive the carrier and operate it, dragging both choline and sodium into the cell

Question 7

Synthesis of transmitter

Answer 7

Acetate made as part of the krebs cycle in the cell is taken up by the mitochondria to make acetyl coenzyme A, which then reacts with the uptaken and Choline and with the help of Choline transferase makes fresh ACh which is then repackaged back inside the synaptic vesicles buy another pump

Question 8

What enzyme helps make fresh acetylcholine

Answer 8

Choline transferase

Question 9

What is the principle of the pump that repackaged the synaptic vesicles

Answer 9

This pump makes use of protons that make it drive acetylcholine inside the cell

Question 10

What is the name of the pump that re packages ACh back inside the synaptic vesicles

Answer 10

VascularAcetylcholine transporter

Question 11

What happens with the disease myasthenia gravis

Answer 11

It interferes the synaptic cleft
the body makes antibodies that recognize ACH receptor
Antibodies bind to the receptors preventing acetylcholine from binding therefore no longer gate their channels reducing the number of receptors that are functional and thus the end plate potential is no longer sufficiently large to go past the threshold to generate an action potential leading to muscle weakness

Question 12

What can be used as a treatment for myasthenia gravis

Answer 12

ACh E inhibitors

Question 13

What drugs can be administered to inhibit the function of a AChE

Answer 13

Edrophonium
Neostigmine
Physostigmine

Question 14

How can inhibiting AChE receptors treat myasthenia gravis

Answer 14

Now that the enzyme is inhibited acetylcholine can last longer in the synaptic cleft and therefore will bind several times increasing the effective concentration of acetylcholine therefore improving transmission therefore causing elevation increasing the amplitude (above threshold) of the endplate potential and leading to successful Nuro transmission in muscle contraction

Question 15

What are the 3 types of Drugs affecting neurotransmission

Answer 15

A)Affecting neurotransmitter synthesis
B) affecting neurotransmitter release
C) affecting postsynaptic cell receptors

Question 16

What drugs affect neuro transmitter synthesis

Answer 16

A)TEC

B) hemicholinium

Question 17

How does TEC work

Answer 17

TEC is taken into the cell preferentially rather than Choline with the help of the Na concentration gradient. Once inside it will take part in the same bio synthetic pathway as choline and bind to acetate to form ATEC. ATEC is the packaged into vesicles by choline transferase and is eventually release from the presynaptic terminal by stimulation of the presynaptic fiber. ATEC, even though it sits on the same binding site on theACh receptor,it’s unable to activate the receptor leading to a very small end plate potential- false transmitter- no amplitude

Question 18

How does hemicholinium work

Answer 18

The drug will bind to the pump and preclude the binding of Choline but itself is not of taken reducing the level of Colin being transported to the inside the cell therefore reducing the level of acetylcholine molecules in the vesicles that fewer molecules are released therefore leading to problems with your level of synaptic transmission leading to transmission failure- Ach reductions amplitude falls short

Question 19

Name to neuromuscular blockers/muscle reluctance

Affect the postsynaptic sites

Answer 19

A) Nondepolarizing competitive blockers

B) depolarizing non-competitive blockers

Question 20

How do you non-depolarizing competitive blockers work

Answer 20

The drug competes with acetylcholine for the same binding site on the receptor the more drug the better chance it has to outcompete ACh. When bound it will not activate the ligand gated receptor therefore no sodium or potassium will flow in therefore leading to no end plate potential no neural transmission and no muscle contraction leading to muscle relaxation

Question 21

How do you depolarizing a non-competitive blockers work

Answer 21

If there is sufficient drug then it will outcompete acetylcholine and bind to the ligand gated receptor, at the initial stage of block it transiently activates the receptor after some time the drug can also pass through the channel and plug it forming a physical block stopping the flow of both sodium and potassium through the channel blocking the transmission, at the later stages of block the inactivation gate can close when the receptor is persistently activated ( this can also happen with ACh)-receptor desensitization

Question 22

Nondepolarizing neuromuscular blockers

Answer 22

In combination with general anesthetic these drugs alone will not cause a loss of consciousness nor a loss of pain but prevent muscle action therefore it is important to have adequate levels of anesthesia as well

Question 23

Examples of non-depolarizing neuromuscular blockers

Answer 23

Tubocurarine, pancorium (muscle relaxant), vecuronium ( muscle relaxant)

Question 24

Examples of depolarizing neuromuscular blockers

Answer 24

Suxamethonium (muscle relaxant), decamethonium