Electrical Excitability Flashcards
What happens when the conductance of any ion is increased
The membrane potential will move closer to the equilibrium potential for that ion
What determines the conductance of an ion
Dependant on the number of channels for the ion that are open
What is the relationship between axon diameter and the increase in sodium ion concentration needed for depolarisation
As the axon diameter increases the concentration decreases. Easier to fire an action potential
What happens in the absolute refractory period
Nearly all sodium channels in the inactivated state
What happens in the relative refractory period
Sodium channels are recovering from inactivation. The excitability returns towards normal as the number of sodium channels in the inactivated state decreases and potassium channels close
Basic structure of voltage gated sodium channel
One alpha subunit which consists of 4 similar sections or repeats
Subunit 4 contains positively charged amino acids which can experiment an electrical field as they are within the membrane. Membrane potential can impose a force on these so when there is a stimulus they detect it and open or close the channel
There is also an inactivation particle
Basic structure of potassium ions
A functional channel composes of 4 alpha subunits
Also have the positive transmembrane segment
How do local anaesthetic work
BH- charged local anaesthetic
B uncharged local anaesthetic
Open channel block, or hydrophillic pathway- block sodium ions from moving through the channel
Hydrophobic block pathway- block sodium channels in the inactivated state
As pain fibres open they are more susceptible to bein blocked by the BH-
What order do local anaesthetics block
Small myelinated axons
Unmyelinated axons
Large myelinated axons
Why is important that sodium channels become inactivated
Enables the repolarisation to occur quickly, also because when they are inactivated they cant open again leading to the refractory period
What is the consequence of the delayed closing of voltage gated postasium ions
Ensure hyperpolarisation as it makes sure the inside f the cell is negative enough to ensure quick recovery of sodium channels from inactivation
Why is the NA/K ATPase not involved i action potential
There is little flow of ions to change the membrae potential
Define capaticance
ability to store charge
a low capiticance is ideal for faster conduction
What is membrane resistance
depends on the number of ion channels open. The lower the resistance the more ion channels are open.
What does high capaticance/ resistance cause
Capaticance- voltage changes more slowly in response to current injection into an axon
Resistance- change in voltage spreads further along the axon
Effect of myelin on the length constant
Increases as it is a good insulator, it enables the local circuit current to depolarise the next node or ranvier above threshold and initiate an action potential
AP jumps from node to node allowing faster conduction velocity
Action potential propagation
- an action potential causes depolarisation of adjacent sections of the axon
- where this local depolarization reaches threshold an action potential is initiated
- the spread of this local change in the membrane potential is increased by a high membrane resistance and low membrane capacitance – the longer this distance the faster the conduction
- myelinated axons have a high membrane resistance and low membrane capacitance
• the action potential jumps from node to node – termed saltatory conduction, which is faster than
that in unmeylinated axons
• damage to the myelin (e.g. in multiple sclerosis) can stop saltatory conduction
Why does calcium influx have such a great effect
Because the concentration of Ca2+ inside is so low, the Ca2+ influx through Ca2+ channels can raise the internal concentration of Ca2+ significantly.
Structure of voltage gated calcium channels
Similar to sodium channels
Transmitter release
- Ca2+ entry through Ca2+ channels
- Ca2+ binds to synaptotagmin- brings vesicles close to membrane of the nerve terminal
- Vesicle brought close to membrane
- Snare complex make a fusion pore 5. Transmitter released through this pore
What is a snare complex
Neurotransmitters fusing with membrane
NAChR
Nicotinic acetylcholine receptor
Ligand acted ion channel
Permable to cations
What is end plate potential
Depolarisation occurs as the resting membrane potential is quite negative [-90mv] close to potassium equilibrium potential but far away from the sodium equilibrium potential. There is a large electrochemical gradient for sodium to move into the cell and potassium out. This is why when ACh binds and opens the channels there is depolarisation
What is neurotransmitters release dependant on
Ca2+ entry
End plate potentials decrease in amplitude as external ca2+ is lowered
What causes local spread of charge in the muscle
Brief depolarisation will activate adjacent Na+ channels due to local spread of charge causing a muscle AP
The AP then initiates contraction of the skeletal muscle fibre this is excitation contraction coupling
Competitive block by d-TC
The d-TC binds competitively to nAChr blocking ACh from binding.
Can be overcome with increasing [] of ACh
Depolarising block of succinylcholine
Succinylcholine isn’t quickly degraded
Succinylcholine opens the sodium ion channels and keeps them open
This maintains depolarisation- then sodium ion channels become inactivated- this fails to activate adjacent Na+ channels besides they gave become inactivated
What is myasthenia gravis
An auto immune disease targeting nACh receptors making them nonfunctional
End plate potential are reduced in amplitude- no AP -leading to muscle weakness and fatigue
Diagnosing myasthenia gravis
Edrophonium prevents ACh esterase from breaking down ACh so it build up in the synaptic cleft
This allows the weakness to be overcome by the increase in amplitude of the endplate potential as there is enough ACh to bind to as many functional nACHr as possible
Organophosphate poisoning
Acetylcholinesterase inhibitors that form a stable irreversible covalent bond to the enzyme
• Recovery from poisoning may take weeks as synthesis of new acetylcholinesterase enzymes is needed
What is the difference between nACHR and mACHhR
Nicotinic produce a fast depolarisation because it is a ligand gated ion channel
Muscuranic produce a slower response because they are coupled to G-proteins which trigger a cascade of events in the cell
what properties of the myelin sheath allow saltatory conduction to occur?
high resistance
low electrical capacity