Neurotransmission Flashcards
Parts of the neuron
Dendrites
Cell body/soma
Axon
Presynaptic terminals
Basic neuron types
Multipolar neuron
Bipolar neuron
Pseudo-unipolar neuron
Unipolar neuron
Axonal transmission
Transmission of information from location A to location B
Synaptic transmission
Integrating/processing of information and transmission between neurons
Neuron’s resting potential
-70 mV
Why is the neurons resting membrane potential negative
Potassium and calcium cross readily
Sodium crosses with difficulty
Large organic proteins (-ve charge) cannot cross
Electrostatic attraction/repulsion
Forces determining distribution of charged ions
Electrostatic pressure
Ions move according to charge
Where are anion proteins mostly found
Restricted to inside the cell
Where are Na+ mostly found
Mostly outside neuron
Where are K+ mostly found
Mostly inside neuron
Where are Cl- mostly found
Mostly outside neuron
Sodium-potassium pump
3 Na+ out for 2 K+ in
Requires ATP- primary active transport
Final resting potential of neuron - -70mV
Na+/K+ pump- results in high Na+ concentration outside but with both force of diffusion and electrostatic pressure pushing in
Membrane and pump resists Na+ inward movement
K+ and Cl- move backward and forward across membrane so reach steady state by opposing forces of diffusion and electrostatic pressure
Some Na+ leaks back in but is expelled by pump
Which forces determine movement of ions across membrane at resting membrane potential
Forces of diffusion
Electrostatic pressure
Events within the action potential
Depolarisation and threshold
Reversal of membrane potential
Repolarisation to resting potential
Refractory period
Synaptic transmission triggers an action potential
Neurotransmitters activate receptors on dendrites / soma
Receptors open ion channels
Ions cross plasma membrane, changing the membrane potential
The potential changes spread through the cell
If the potential changes felt at the axon hillock are positive (+mV), and large enough, an action potential is triggered
Where do neurotransmitters initiate a change in membrane permeability
Dendrites of neurones
Excitatory neurotransmitters
Depolarise the cell membrane
Increase probability of an action potential being elicited
Cause an excitatory post synaptic potential
Inhibitory neurotransmitters
Hyperpolarise the cell membrane
Decreases probability of an action potential being elicited
Cause an inhibitory post synaptic potential
The action potential at an EPSP
EPSPs begin to depolarise cell membrane
Threshold ~ -60mV
When reached Na+ channels open (Na+ rushes in) and polarity reverses to +30 inside
Membrane potential reverses with the inside going positive
…at which point voltage-gated Na+ channels close and K+ channels open (K+ rushes out)
…which restores resting membrane potential
Threshold value
-60 mV
Propagation of the action potential
Signal loss due to lack of insulation –could be overcome by continual opening of next ion channel
But SLOW due to time to activate each channel.
Mainly short axon interneurons
Saltatory conduction
Decremental conduction between nodes of Ranvier (but ‘re-boosted’ each time)
But very fast along axon.
Most CNS neurons.
2 ways to reach threshold at inhibitory post synaptic potentials
Spatial summation
Temporal summation
Spatial summation
simultaneous signals coming from multiple presynaptic neurons being received by a single postsynaptic neuron
Temporal summation
involves a single presynaptic neuron rapid-firing signals to a postsynaptic neuron
Symptoms of multiple sclerosis
Eye movements – uncontrolled, seeing double
Speech – slurred
Paralysis – partial/complete, any part of body
Tremor
Co-ordination – lost
Weakness – tired
Sensory – numbness, prickling, pain
Diagnosis of multiple sclerosis
Initial symptoms – slight with remission…
….becoming more numerous, frequent and severe
Difficult to diagnose:
Early symptoms slight – person doesn’t go to doctor
Other diseases have similar symptoms
No definitive test: repeated presentation of symptoms combined with MRI
Who is affected by multiple sclerosis
Young adults 20-40
Slightly more women than men
Temperature zones
Areas with high standards of sanitation
Chemical synapse
- Action potential arrives at presynaptic knob and depolarises membrane
- Voltage activated Ca2+ channels open and influx of Ca2+
- Causes vesicles contains neurotransmitter to fuse with membrane and release neurotransmitter by exocytosis
- Diffuses across synaptic cleft
- Neurotransmitter binds to receptors on postsynaptic membrane causing Na+ channels to open
- Influx of Na+ causing depolarisation of membrane
Size of synaptic cleft
20-30 nm
After binding to postsynaptic knob, what happens to the neurotransmitter
Enzyme degradation
Reuptake into presynaptic knob
Acetylcholine
key neurotransmitter at the neuromuscular junction – it activates muscles
Not just skeletal muscles (for voluntary movement), also heart, respiratory muscles, gastrointestinal tract, eye muscles, muscles around blood vessels………
Symptoms of novichok poisoning as for many other nerve agents (which usually also target the ACh system)
Excessive activation of muscles (convulsions) initially
Subsequent paralysis as muscle cannot continually contract
Failure of heart muscles (heart failure)
Failure of muscles controlling respiration (asphyxsiation/drowning)
Failure of muscles in eye (pupils constricted / paralysis)
Failure of skeletal muscles (paralysis)
Failure of muscles of digestive tract (vomiting/diarrhoea)
Treatment of nerve agent poisoning
Atropine is an ACh receptor blocker – but doses needed to be effective very high (side effects)
Drugs which can re-activate AChE may also be administered
Usually intensive life-support required (due to cardiovascular effects)
Long-term damage of neuromuscular function probable
5 fundamental processes of synaptic transmission
Manufacture- intracellular biochemical processes
Storage - vesicles
Release- by action potential
Interact with post-synaptic receptors- diffuse across synapse
Inactivation- break down or re uptake
Common fast neurotransmitters- short lasting effects
Acetylcholine (ACh)
Glutamate (GLU)
Gamma-aminobutyric acid (GABA)
Common neuromodulators - slower timescale
Dopamine (DA)
Noradrenalin (NA) (norepenephrine)
Serotonin (5HT) (5-hydroxytryptamine)
Mechanism of local anaesthetics (procaine and lignocaine)
Na+ channels blockers - particularly well absorbed through mucous membranes
Blocks progress of action potential
ACh is affected by
Cigarettes (nicotine - agonist)
Poison arrows (curare - antagonist)
Spider toxins (black widow - release)
Nerve gas (WW-I – blocks break-down)
Noradrenaline is affected by
Antidepressant drugs (Imipramine – blocks re-uptake)
Antidepressant drugs (MAO inhibitors – block break-down)
Stimulants (Amphetamine – increases release and blocks re-uptake)
Where is noradrenaline commonly found
Peripheral (heart) and central nervous system
Where is dopamine an important transmitter
Basal ganglia
Dopamine transmission affected by
Antipsychotic drugs (Chlorpromazine – receptor blocker)
Stimulants (Amphetamine/cocaine – increase release and block re-uptake)
Anti-Parkinson drugs (L-DOPA increases manufacture
Serotonin transmission is affected by
Antidepressant drugs (Prozac – serotonin re-uptake inhibitor – SSRI)
Hallucinogens (LSD, psilocybin –5HT receptor agonist)
Ecstasy (MDMA, increase release, reduce reuptake)
How do hallucinogenic drugs work
mimic serotonin, and can activate numerous different serotonin receptor subtypes
But the hallucinogenic effect itself appears to be specifically related to the way they target the serotonin ‘2a’ receptor (5-HT2a)
Examples of hallucinogenic drugs
LSD
Magic mushrooms
Ketamine
Gamma-aminobutyric acid affected by
Anti-anxiety drugs (benzodiazepines - valium – inhibitory effect at GABA receptors
Anticonvulsant drugs (benzodiazepines – see above)
Anaesthetics (Barbiturates – potentiate the effect of GABA
Side effects of GABA agonists
Anti-anxiety
Anti-convulsant
Anaesthetic
Side effects of L-DOPA
Anti-parkinson
Causes psychosis at high doses
Side effects of dopamine blockers
Anti-psychotic
Causes Parkinson-symptoms at high doses
Problems for drug design
A region of the brain engaged in a particular function uses several neurotransmission systems e.g. basal ganglia
Glutamate
GABA
Dopamine
Acetylcholine
Substance P
Enkephalin
Regions of the brain engaged in different functions use the same neurotransmission systems
Glutamate
GABA
Acetylcholine
Serotonin
Dopamine/Noradrenalin
Mechanism of novichok
Disrupts normal synaptic transmission of acetylcholine
Local currents
Action potentials propagated along axons via local currents
Flow following depolarisation and allow depolarisation of adjacent axonal membranes
Why does the local current only flow in one direction
Refractory period
Capacitance
Ability to store charge
Lower capacitance = greater distance travelled
Resistance
Number of ion channels open
Higher resistance (less channels open) = greater distance travelled
What decreases capacitance
Myelin
What is the distance an action potential travels dependent on
Capacitance and resistance
Greater distance travelled
Lower capacitance
Higher resistance
Absolute refractory period
Another action cannot be generated again under any circumstances
Relative refractory period
Another action potential can be fired if the stimulus is strong enough
What is myelin stained with
Osmium - white matter turns black
Myelin is composed of
70 % lipid
30% protein
Which cells produce myelin sheath in CNS
Oligodendrocytes
How many axons can a single oligodendrocytes myelinate
50
Which cells myelinate axons in the PNS
Schwann cells
How long of a segment does a single Schwann cell myelinate
1.5mm
How is the myelin sheath formed
Concentric wrapping of cell membranes —> from 20 to 200 layers
When does myelinated begin
During 3rd trimester
Progresses rapidly during infancy
Continues through adolescence
Where are unmyelinated neurones commonly found
In post-ganglionic autonomic fibres and olfactory neurones and interneurones eg hypothalamus
Where are myelinated neurones typically found
Somatic nerves
How does myelination improve conduction
Increases resistance
Decreases capacitance
Node of Ranvier
Periodic gaps along myelinated axon
High density of ion channels
Action potentials happen here
Guillain-Barré syndrome
Rapid onset of muscle weakness
Caused by autoimmune damage to PNS- damages myelin sheath
Symptoms of Guillain-Barré syndrome
Pain and weakness
Typically begins in feet and hands
Spreads proximally.
Where are electrical synapses found
Brainstem neurons eg hypothalamus
Hormone secretion
Electric synaptic transmission
Plasma membranes of pre and postsynaptic cells are joined by gap junctions
Local currents flow directly across junction through connecting channels
Depolarises membrane of 2nd neuron to threshold propagation
Very rapid communication
Types of post-synaptic receptors
Ionotropic receptors
Metabotropic receptors
Iomotropic receptors
Ligand gated ion channels
Allows ion flux, changing cell voltage
Speed of response in ionotropic receptors
Rapid
Length of response in ionotropic receptors
Short-acting
Metabotropic receptors
G protein coupled receptors (GPCRs)
Acts through secondary messengers, causing cellular effects
Speed of response of Metabotropic receptors
Slow
Length of response of Metabotropic receptors
Prolonged resposne
Action of neuromodulators
Cause change in synaptic membrane that’s longer lasting
Tend to be slower events eg learning and development
Examples of neuromodulators
Dopamine
Noradrenaline
Serotonin
2 types of ACh receptors
Nicotinic
Muscarinic
Nicotinic receptors respond to
ACh and nicotine
Nicotinic receptors are found in
Neuromuscular junctions
Nicotinic receptors
Contain ion channels that open in response to ACh
Nicotinic receptors in the brain
Important in cognitive function and behaviour
Muscarinic receptors are present in
Brain
Where PNS innervates peripheral glands and organs eg salivary glands, Bronchoconstriction
Muscarinic receptors
Receptors coupled with G proteins
Not ion channel- instead trigger signalling pathways in the target cell that inhibit action potentials
What is the main excitatory neurotransmitter
Glutamate
What is the main inhibitory neurotransmitter
GABA
How does imipramine affect noradrenaline
Blocks reuptake
Antidepressant
How does monoamine oxidase affect noradrenaline
Increases amount of noradrenaline by inhibiting MAO (which breaks it down)
Antidepressants
How does amphetamines affect noradrenaline
Increase release and block reuptake
Stimulant
How does amphetamines affect dopamine
Increase release and block reuptake
How does L-DOPA affect dopamine
Increases manufacture
Parkinson’s medication
How does chlorpromazine affect dopamine
Antagonist and blocks receptors
Antipsychotic drugs
How does Prozac affect serotonin
Increases concentration of synaptic serotonin- selective serotonin reuptake inhibitor
Antidepressants
How does ecstasy affect serotonin
Neurotoxic to serotonin neurones- destroys the terminal of axons
Length of refractory period
5-10ms
Tonic receptors
slow adapting receptors. They will respond to the stimulus as long as it persists, and produce a continuous frequency of action potentials. Hence, they convey information about the duration of the stimulus
Phasic receptors
rapidly adapting receptors. They will respond quickly to stimuli but stop responding upon continuous stimulation. Therefore, action potential frequency decreases during prolonged stimulation. This class of receptor conveys information about the changes to the stimulus such as intensity.
What affects conduction velocity
Myelination
Diameter
Membrane capacitance
Membrane resistance
Membrane capacitance
Ability to store charge
Lower capacitance = greater distance travelled before threshold no longer reacher
Membrane resistance
Depends on number of ion channels open
Lower number channels open = greater membrane resistance = greater distance travelled before threshold no longer reached
How does myelination speed up conduction velocity
Decreases membrane capacitance
Increases membrane resistance
Saltatory conduction
