Cellular Response To Action Potential (5.1) Flashcards
What is a key feature of Ca channels?
Are very selective – will only let calcium through
How do action potentials open calcium channels in cell membranes?
Depolarisation at the nerve terminal causes voltage gated Ca channels to open.
Calcium enters the cell and causes the intracellular levels of Ca to increase.
The increase in intracellular calcium levels causes neurotransmitters to be released.
How do the levels of calcium differ from those of other ions in the cell membrane?
The intracellular concentration of calcium is so low that th inflow of Ca ions raise the levels significantly.
Describe the structure of calcium channels
Four repeated subunits which wrap around to form an aqueous pore.
Have numerous isoforms which are found in different locations throughout the body and have different blockers
What is the most common calcium channel and what blocks it?
Alpha (1C,D,S) – type L
Found in all muscles, neurones and in lungs
Blocked by dihydropyridines e.g. Nifedipine
What components make up a functional channel?
Pore forming subunit is needed for a functional channel
Other subunits modify properties to allow for correct regulation
E.g. Glycosylation and phosphorylation sites
What process occurs to release neurotransmitters?
Exocytosis
Describe the structure of the neuromuscular junction and give the neurotransmitter and what removes it
Has a short synaptic cleft to allow for rapid diffusion
ACh is broken down quickly by acetylcholinesterase
– [ACh] is increased quickly, then removed quickly
Describe the process of transmitter release.
Ca enters through voltage gate calcium channels
Ca binds to synaptotagmin
Vesicles are brought close to the membrane
Snare complex changes conformation to make a fusion pore
The transmitter is released through the pore
What assists in efficient transmission?
Ca channels are located close to the vesicles release sites so exocytosis will occur quickly
What does binding of ACh to nicotinic receptors cause?
Binding of 2 ACh molecules causes nicotinic ACh rceptors to open.
They are cationic channels –> aren’t very selective
When ACh leave then channels close
The channel produces a fast depolarisation due to Na gradient
– it produces an end plate potential, which raises the mule above threshold to produce an action potential
What do competitive blockers do?
Competitively block nicotinic ACh receptors by binding at the molecular recognition site
Give the name of a competitive blocker and what it does
Tubocurarine
Sits in receptor site but does not stimulate the opening of an ion channel or the binding of ACh
– causes muscle paralysis
Give the name of a depolarising blocker and how it blocks the receptor
Succinylcholine
- causes a maintained depolarisation which fails to activate Na+ channels (are in inactivated state – accommodation)
- opens the channels, but are desensitized
What is the normal depolarisation mechanism of ACh binding?
A brief depolarisation will activate adjacent Na channels due to local spread of charge. This causes an action potential to be generated.
What are miniature end plate potentials?
Small depolarizations which do not reach threshold
– they correspond to spontaneous release of vesicles which measure at about 1 mV
What is myasthenia gravis?
What does it cause?
An autoimmune disease which targets nicotinic ACh receptors
Sufferers have profound weakness which increase with exercise
What causes myasthenia gravis?
What happens to end plate potentials?
Causes by antibodies which are directed against nicotinic ACh receptors on the post synaptic membrane of skeletal muscle.
They cause a decrease in the number of functional receptors due to:
Complement mediated lysis and receptor degradation
End plate potentials are reduced leading to muscle weakness and fatigue
Less receptors are available which causes a smaller response
Give a treatment for myasthenia gravis and how it helps
Acetylcholinesterase inhibitors
– can improve the action potential conduction
How do end plate potentials generate an action potential?
End plate potentials depolarise adjacent muscle membrane which activates voltage gated Na channels.
This initiates an action potential in the muscle fibre which will contract due to excitation-contraction coupling
Describe a nicotinic acetylcholine receptor, where it is found and what it generates.
It is a ligand gated ion channel
Found in skeletal muscle and in preganglionic neurones
It causes fast depolarisation
Describe muscarinic ACh receptors
Have no ion channels – are g-protein coupled which causes a cascade of events inside the cell therefor giving a slower response than with nicotinic a receptors
