Neural Signalling Flashcards
What is the Hodgkin & Huxley experiment?
Placing electrodes inside a neurone allows measurement of the potential difference between the inside and the outside of the cell
What is the resting potential of a neurone?
-65 mV
How do intracellular proteins contribute to the resting membrane potential?
There are large proteins within the cytoplasm that are too large to pass through channels in the membrane
They have a predominance of negatively charged groups on their surface
The lack of membrane permeability means the proteins are trapped within the cell, making it increasingly negatively charged
How does the sodium/potassium ion pump contribute to the resting membrane potential?
It moves 3 Na+ ions out of the cell for every 2 K+ ions it allows in
The inside of the cell becomes increasingly negative
What is the potassium ion gradient?
Potassium ions tend to diffuse out of the cell down a concentration gradient through K+ selective channels
How does the potassium ion gradient contribute to the resting membrane potential?
The large negatively charged protein molecules trapped in the cell cause an electrical gradient that tends to pull K+ ions back into the cell
The fluxes become balanced so that K+ distribution is in equilibrium
What is the potassium equilibrium potential?
Why is it not the same as the resting membrane potential?
-70 mV
The small leakage of sodium ions means the values are slightly different
How do you determine the equilibrium potential for any ion?
Use the Nernst Equation
How do sodium ion gradients influence the resting membrane potential?
Both the concentration and electrical gradients operate in the same direction to cause an inward flow of ions
This brings the resting membrane potential back up to -65 mV
Why may some neurones have resting potentials outside of the normal range?
Variation is due to differing levels of expression of ion channels in the membrane
Relative permeability of ions depends on the number of channels in the membrane through which ions can pass
What is an action potential?
It is an explosion of electrical activity created by a depolarising current
It is the means by which a neurone sends information down its axon, away from the cell body
What happens during the resting state of an action potential?
All the voltage-gated Na+ and K+ channels are closed
They remain closed until the threshold potential is reached
What happens once Na+ channels open?
Sodium ions enter the cell
The cell becomes depolarised as the membrane potential rises towards zero
What is the threshold potential and what happens when it is reached?
-40 mV
If it is reached, voltage-gated Na+ channel activation gates start to open
Na+ ions enter the cell, causing it to be more positive and open more activation gates
Large influx of Na+ ions leads to an action potential spike
What happens after the action potential spike?
Na+ channels close when Na+ equilibrium potential is reached which is +65mV
Inactivation gates begin to close as the interior of the cell becomes less negative
Voltage-gated K+ channel activation gates start to open and K+ ions flow out of the cell
What happens during repolarisation?
The membrane potential is reversed as K+ ions leave the cell
What happens during hyperpolarisation?
K+ ions continue to flow out of the cell whilst the Na+ channel inactivation gates are fully closed
This leads to the refractory period where no action potentials can be generated
How is resting potential re-established?
When the flow of ions stops, the ions are redistributed across the membrane by Na+/K+ pump
What is the example of positive feedback in the action potential?
The nerve cell only depolarises if it reaches the threshold potential
Voltage-gated Na+ channels open and more Na+ enter the cell
What is meant by the “all-or-nothing” response?
For each type of nerve cell, the amplitude of the action potential, the resting potential and the threshold potential are constant
What happens to the action potential if the stimulus intensity is increased?
The amplitude of the action potential will NOT change
There is a higher action potential frequency
There is a shorter latency period between the stimulus and the action potential
Why is the refractory period important?
It means that an action potential can only travel in one direction and cannot travel back towards its point of origin
What is the absolute refractory period?
No further action potentials can be elicited no matter how large the stimulus is
This ensures action potential propagation is unidirectional
What is the relative refractory period?
During this period, a larger stimulus can result in an action potential
Initiation of a second action potential is inhibited, but not impossible
How is an action potential propagated in a non-myelinated neurone?
Na+ influx will depolarise an area in the neurone and trigger voltage-gated Na+ channels to open further along
This generates an action potential in the next membrane segment
How is an action potential propagated in a myelinated neurone?
Local currents can only flow in and out of the axon at the nodes of Ranvier
This is the only area where the membrane can depolarise
The action potential “jumps” between the nodes of Ranvier by saltatory conduction
What is a sensory modality?
It is what is perceived after the stimulus
“sense”
What is sensory transduction and why is it needed?
It is the conversion of environmental or internal signals into electrochemical energy
All stimuli must be converted to electrochemical energy in order to be transported along the axon
What is a receptor potential?
The transmembrane potential difference produced by activation of a sensory receptor
It is a graded potential that causes an action potential if the threshold is reached
How are specific signals decoded in the CNS?
Through the rate and pattern of action potential firing
What are muscle spindles?
A bunch of modified skeletal muscle fibres (intrafusal fibres) enclosed in a connective tissue capsule
How do muscle spindles prevent the muscle from being over-stretched?
Intrafusal fibres detect stretch and initiate a reflex that causes the muscle to contract
How does action potential frequency change when the muscle spindle is activated?
When a muscle is stretched passively the spindle is activated and initiates a reflex
Action potential frequency increases during stretch
When the muscle contracts and shortens, the reflex is switched off
Action potential frequency declines during contraction
How is the knee-jerk reflex initiated?
Striking of the patellar ligament with a reflex hammer just below the patella
This stretches the intrafusal fibres of the muscle spindle in the quadriceps muscle
How is the knee-jerk reflex conducted after the muscle spindle is stretched?
Stretching the muscle will stretch the spindle and increase discharge of the sensory neurones
Increased firing of the motor neurone
The quadriceps muscle contracts
What is significant about the knee-jerk reflex?
There is no spinal interneurone
The bipolar sensory neurone synapses directly on a motor neurone in the spinal cord
What is the role of the inhibitory interneurone in the knee-jerk reflex?
It is involved in relaxation of the antagonistic hamstring muscle
This helps to dampen the stretch of the muscle
What is the Golgi Tendon organ and where is it found?
It is located in the tendon
It responds to tension
It is stimulated when the associated muscle contracts or is stretched and protects the muscle against excess load
What is the structure of the Golgi Tendon organ?
Small bundles of tendon fibres (collagen) enclosed in a layered capsule
The terminal branches of a large diameter afferent fibre are intertwined with collagen bundles
What is the reflex inhibition set up by the GTO?
It sets up a reflex that causes muscle to relax
This removes stimulation
When is GTO active?
During both passive stretch and active contraction
What type of receptors are muscle spindles and the GTO?
They are both proprioceptors and mechanoreceptors
What are the two different types of synapses and how do they work?
Electrical synapses direct a passage of current via ions flowing through gap junctions
Chemical synapses release vesicles containing neurotransmitter which has an effect on receptors on the target cell
How do gap junctions result in fast electrical transmission between neurones?
Gap junctions are present at points of contact between neurones with no synaptic cleft
There is only a very narrow gap between their membranes
Ions can pass directly from one cell to the next
What are gap junctions formed by?
They are formed by channels called connexons
What is the role of connexons?
They form pores that allow the cytoplasm of the two cells to be in continuity
The pores have some selectivity over ions and small molecules that can pass through
What are connexons made of?
Protein molecules called connexins
How are neurotransmitters released from the presynaptic neurone?
Action potential reaches the terminal bouton of the presynaptic cell
Voltage gated Ca2+ channels open and calcium enters the cell
Calcium influx causes the vesicle and synaptic membranes to fuse
Neurotransmitters are released into the synaptic cleft
Why are vesicles docked and primed before the action potential arrives?
They are kept close to the plasma membrane
This allows release to be as rapid as possible upon increase in calcium concentration
How can the probability of neurotransmitter release be increased and decreased?
Increased by increasing calcium concentration
Decreased by blocking depolarisation of the membrane and preventing calcium influx
What happens once the neurotransmitter is released?
It diffuses across the synaptic cleft to act on specific receptors on the postsynaptic membrane of a cell body or dendrite
How do postsynaptic receptors alter the properties of the postsynaptic cell?
They open gated ion channels
This allows action potential signals to be communicated from one neurone to the next
What is a neurotransmitter?
A substance shown to be released by a neurone and have a physiological action on specific receptors on a target cell
What is a neuromodulator?
A substance that is released and modifies the action of a neurotransmitter
What is a neuroactive substance?
A neutral term for a substance that is known to have an effect on the CNS
Its precise action is not known
What are the amine neurotransmitters?
dopamine noradrenaline adrenaline histamine serotonin
what are the amino acid neurotransmitters?
gamma-aminobutyric acid (GABA)
glutamate
glycine
what are the peptide neurotransmitters?
dynorphin enkephalins neuropeptide Y calcitonin gene-related peptide (CGRP) somatostatin galanin substance P thyrotropin-releasing hormone vasoactive intestinal polypeptide
What are active zones? What is found there?
specialised areas on the presynaptic membrane
they guide the vesicles towards the membrane in a calcium-dependent fashion
synaptic boutons contain voltage-gated calcium channels near the active zone
What is the process of docking?
Vesicles release their contents by exocytosis when the membrane of the synaptic vesicle fuses to the presynaptic membrane at the active zone
How does priming allow for a rapid release of neurotransmitter?
Ca2+ enters the axon terminal directly at the active zone
This is precisely where the vesicles are primed for exocytosis
What is significant about the local microdomain around the active zone?
It allows calcium to reach high concentrations
How is the fused membrane vesicle taken back into the cell?
Endocytosis
What does an ionotropic receptor comprise?
Ion channel that comprises 4 or 5 similar protein subunits arranged around a central pore
What happens when a neurotransmitter binds to an ionotropic receptor?
It causes a conformational change that will briefly open the central pore
Ions can pass through and cause a rapid change in the resting potential of the cytoplasm
How fast is the response from an ionotropic receptor?
They provide rapid responses
The movement of ions will depolarise or hyperpolarise the postsynaptic cell
What is a metabotropic receptor comprised of?
Single, long protein molecule with 7 transmembrane domains
It has no ion pore
What happens when a ligand binds to a metabotropic receptor?
There is a conformational change in the molecule, causing the intracellular part to interact with a G-protein
There is a chain of intracellular events that may lead to the opening of ion channels
How fast is the response of a metabotropic receptor?
Much slower than ionotropic receptors
What is an excitatory transmitter receptor?
It allows an influx of Na+ when it is activated
This causes a net inwards current and results in an EPSP
What is an EPSP?
What does it do?
Excitatory postsynaptic potential
It brings the postsynaptic cell closer to the threshold for firing action potentials by depolarising it
Give two examples of excitatory transmitters
Glutamate and acetylcholine
What are inhibitory transmitter receptors?
They allow the efflux of K+ or influx of Cl- once activated
This causes a net outward current and leads to an IPSP
What is an IPSP?
What does it do?
Inhibitory postsynaptic potential
It brings the postsynaptic cell further away from the threshold for firing action potentials by hyperpolarising it
What happens to the EPSP/IPSP if a greater amount of transmitter is released?
More transmitter leads to more ion channels opening and a greater current flow
This leads to a greater IPSP/EPSP due to summation of individual presynaptic potentials
How is an action potential related to an IPSP/EPSP?
One action potential will only cause a single EPSP/IPSP
Many action potentials will reach the threshold value and initiate an action potential in the postsynaptic neurone
How is determined whether an action potential will fire in the postsynaptic neurone?
The same neurone can receive many excitatory and inhibitory inputs
It is the balance of the EPSPs and IPSPs that determine whether it will fire an action potential
How do glial cells play a role in terminating the action of a neurotransmitter?
The transmitter can be taken up into glial cell processes lining the peri-synaptic zone by glial cell transporters
It is then shuttled back into neurones
Or it is broken down or converted by enzymes in the glial cells
The resulting metabolites are shuttled back into neurones
How can a neurotransmitter’s actions be terminated in the synaptic cleft (not involving glial cells)?
It can be taken back up directly into neurones by transporters on the presynaptic membrane
It can be broken down by cell surface enzymes into constituent parts
