Presynaptic Inhibition Flashcards
Role of the Na+/K+ ATPase pump
Actively pump three Na+ out and K+ into the cell
Depolarised internal environment
Two types of channels
Voltage gated
Leak
Role of the sodium channel
Rapid influx of sodium into the cell upon opening resulting in depolarisation
Role of potassium channels
Permits rapid efflux of potassium out of the cell causing hyperpolarisation
What is the resting membrane potential
-70mV
What two forces do ions act under
Electrostatic force (depends on charge)
Force of diffusion (concentration)
Action potential steps
1) resting membrane potential
2) depolarisation stimuli via graded potential
3) depolarisation reaches threshold NaV open and sodium ions enter (VGSC open at the axon hillock)
4) rapid Na+ entry further depolarises the neuron
5) Nav channels inactivate and slower potassium (0.5ms) Kv channels open
6) potassium ions move out of neuron, it becomes negative
7) Kv channels remain open, more potassium leaves neurons causing hyperpolarisation
8) Kv channels close, some potassium ions enter via leak channels
9) normal resting membrane potential
Synaptic transmission
AP arrives
VGCC open
Calcium ion influx
Vesicles bind to post synaptic membrane
Exocytosis of vesicles
NT diffuses across synaptic cleft and activates post synaptic cell
What does more APs cause
More NT release
Excitatory and inhibitory inputs on the post synaptic neuron
Excitatory - neuron depolarises
Inhibitory - neuron is hyperpolarised and decreases the firing potential
In reality - combination of both
Graded potential
Not all or nothing (stronger stimulus correlates to a larger change in membrane potential)
Rapid decay
Post synaptic channel opens, membrane potential spread through cytoplasm and diminishes over time (ripple effect)
Triggering an AP in the postsynaptic cell
Channels of postsynaptic cell open causing depolarisation
Depolarisation travels to the AIS (densely packed VGSC population)
Depolarisation needs to reach threshold to generate an AP
If threshold reached - all or nothing AP
Spatial summation
Multiple inputs from presynaptic neurons synchronously summate to trigger an AP
Temporal summation
Multiple signals synchronously fire and summate to cause an AP
Normal functioning synaptic modulation
- Excitatory neuron fires (glutamate)
- AP is generated
- Signal is passed to all targets
- Postsynaptic response is initiated
Steps in presynaptic inhibition
1) An excitatory neuron fires
2) a graded EPSP causes AP
3) inhibitory neuron fires preventing NT release at 1 synapse (giving rise to a hyper polarising current)
4) postsynaptic response in the rest of the synapses
Steps in postsynaptic inhibition
1) both an excitatory and inhibitory neuron fire
2) below threshold graded potential
3) no AP generated
4) no response elicited at any target
What does presynaptic inhibition cause
More specific control
Precise inhibition of specific synapses
What does postsynaptic inhibition cause
General inhibition
All synapses are inhibited equally
Why is presynaptic inhibition important
The spinal cord is the neural interface between the brain and the body
It is constantly receiving information via primary afferent fibres
It prevents excessive excitation by filtering out weak or irrelevant signals
Monosynaptic stretch reflex Eccles et al., 1961
La afferent from the muscle spindle to the SC could be depressed
No change in motoneuronal membrane potential
No change in motoneuronal excitability or ionic permeability
Inhibition must be presynaptic via stimulation of knee flexors,posterior biceps and semitendinosus
What is primary afferent depolarisation PAD
Reduces afferent neurotransmission
Via depolarisation of afferent terminals
Causes reduced NT release likely via GABAergic inhibitory inter neurons
Axo axonic synapses
Modulate NT release
Usually GABAergic (inhibitory interneuron on the presynapse) decrease the amount of NT released
IPSP
Ionotropic GABAaR open
Causes Cl- ion influx (hyperpolarising stimuli)
Chloride equilibrium in PAD
Na+ K+ Cl- cotransporter keeps Cl- potential less negative than the Membrane potential
GABAaR activation causes Cl- efflux and depolarisation
What is the Dorsal root potential DRP
Afferent stimulation evoked GABAa receptor activation, Cl- leaves
Primary afferent depolarisation
Dorsal root potential (summed back propagated PAD from many axons)
How to record DRP
Proximal electrode of a pair on the root outside of the cord sees a more negative potential
Negativity decays electrotonically
Creates extra cellular negativity (Cl- efflux)
Terminal is depolarised
How does PAD inhibit NT release
Inactivates VGCC
Voltage dependent inactivation of NaV
Shunting of conductance (GABAa channel open but net ion flow is 0)
What is shunting inhibition
Cl- ion channels are opened
Leakage of signal, membrane is more leaky to current
Reduces net depolarisation by excitatory synapses
Name GABAa blockers
Picrotoxin and bicuculline
