Synaptic Transmission Flashcards
Describe what happens when the action potential reaches the axon terminal- Bhutan
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
What does the endplate potential depends on
It depends on the amount of acetylcholine release and the number of acetylcholine receptors activated therefore giving rise to a graded amplitude
What happened to acetylcholine molecules after the electrical impulse is transmitted to the postsynaptic cell
ACh molecules disengage and unbind from the acetylcholine receptors and go back into the synaptic cleft where they are scavenged by an enzyme - acetylcholinesterase
What does acetylcholinesterase do
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
What happens to acetate
It diffusers away and it’s not retained at the synapse
What happens to Choline
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
Synthesis of transmitter
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
What enzyme helps make fresh acetylcholine
Choline transferase
What is the principle of the pump that repackaged the synaptic vesicles
This pump makes use of protons that make it drive acetylcholine inside the cell
What is the name of the pump that re packages ACh back inside the synaptic vesicles
VascularAcetylcholine transporter
What happens with the disease myasthenia gravis
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
What can be used as a treatment for myasthenia gravis
ACh E inhibitors
What drugs can be administered to inhibit the function of a AChE
Edrophonium
Neostigmine
Physostigmine
How can inhibiting AChE receptors treat myasthenia gravis
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
What are the 3 types of Drugs affecting neurotransmission
A)Affecting neurotransmitter synthesis
B) affecting neurotransmitter release
C) affecting postsynaptic cell receptors
What drugs affect neuro transmitter synthesis
A)TEC
B) hemicholinium
How does TEC work
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
How does hemicholinium work
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
Name to neuromuscular blockers/muscle reluctance
Affect the postsynaptic sites
A) Nondepolarizing competitive blockers
B) depolarizing non-competitive blockers
How do you non-depolarizing competitive blockers work
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
How do you depolarizing a non-competitive blockers work
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
Nondepolarizing neuromuscular blockers
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
Examples of non-depolarizing neuromuscular blockers
Tubocurarine, pancorium (muscle relaxant), vecuronium ( muscle relaxant)
Examples of depolarizing neuromuscular blockers
Suxamethonium (muscle relaxant), decamethonium
