How nerves work Flashcards
What are the three subdivisions of the nervous system?
Brain, Spinal cord and peripheral nerves
How many spinal nerves exist?
31
What does the grey matter contain?
Cell bodies
What does the white matter contain?
Axons covered in myelin
What nerve fibres does the dorsal root contain?
Sensory / afferent nerves to spinal cord
What nerve fibres does the ventral root contain?
Motor/ efferent nerves from the spinal cord
Where in a neutron is the critical threshold region?
Axon hillock
Are the interneurons part of the CNS or PNS?
CNS
What type of cells contribute to 90% of the cells in the CNS?
Glia (astrocytes, oligodendocytes, microglia, ependymal)
Describe the general structure of the neuron.
Cell body (soma), axon, dendrites, axon hillock, axon presynaptic terminal, myelin sheath, Schwann cells
Describe the ionic basis of the resting membrane potential.
Generated by K+ permeability (hence close to K+ equilibrium potential of -90mV)
What does the nearest equation predict?
The membrane potential at which the electrical gradient is equal and opposite to the concentration gradient.
What other ions does the RMP have a small but significant permeability to?
Sodium and Chlorine
What is the action of the sodium and potassium pump?
Pumps 2 x K+ into the cell and 3 x Na+ out.
Why is the resting membrane potential equal to -70mV and not -90mV?
Other “leaky” channels and electrogenic nature of the Na/K pump.
When do you lose the RMP?
When the concentration runs down.
What is the only concentration gradient that is greater inside the cell?
K+
What concentration gradients are greater outside of the cell?
Na+, Cl-, Ca2+
What is the only electrical gradient that is greater inside the cell?
Cl-
What direction does the electrical gradient flow for K+, Na+ and Ca2+?
From outside of cell to inside of cell.
Draw a graph to show overshoot, replorising, depolarising, and hyperpolarising.
Depolarising = from -70mV towards 0 Repolarising = from 50mV towards 0 Overshoot = from 0 to 60mV Hyperpolarising = from -70mV to -90mV
Describe the ionic basis of the action potential.
Mediated by voltage-gated channels and the influx of sodium inside the cell down a concentration gradient.
What are the characteristics of the action potential?
- Only fire at threshold
- All or none
- Self propagating
- Non-decremental
Describe the stages of an action potential.
- Depolarisation at one end of the axon.
- Voltage gated sodium channels open
- Sodium flows down concentration gradient
- Massive depolarisation
- K+ permeability slowly rises
- Repolarises to K+ equilbrium
- Hyperpolarise
- K+ channels close
Why can an AP not travel backwards?
Absolute refractory period.
Define compound action potential.
Extracellular recording from a bundle of axons (nerve trunk).
How are fibres classified?
According to conduction velocity and function of axons.
What are the largest fibres?
Aalpha - proprioception and motor neurons
What are the smallest fibres?
C - heat, “slow” pain
Name all of the types of fibres.
Aalpha, Abeta, Agamma, Adelta, B, C
What type of fibres are most sensitive to pressure and least sensitive to local anaesthetic?
Aalpha (largest) fibres
What type of fibres are least sensitive to pressure and most sensitive to local anaesthetic?
C (smallest) fibres
Define the relationship between conduction velocity and fibre type.
Larger fibres = fastest conduction velocity
Smaller fibres = slowest conduction velocity
Give two examples of de-myelinating diseases.
Multiple sclerosis and Guillain-barre syndrome
Describe the consequences of de-myelinating disease.
- Resistance of membrane is lower and capacitance is higher (i.e higher ability to store charge)
- Big local current delays quicker
- Does not depolarise to next node to threshold
- Conduction fails
Describe the structure of the NMJ.
Motor nerve fibre, myelin, Schwann cells, axon terminal with calcium voltage gated channels, mitochondria and synaptic vesicles containing acetylcholine, active zone, synaptic cleft, sarcolemma and junctional folds, acetylcholinesterase, Na+ channels, acetylcholine nicotinic receptors.
Describe the 10 step process of neuromuscular transmission.
- AP in motorneuron (Na+ channel influx)
- Calcium voltage-gated channels open and influx of calcium into pre-synaptic terminal
- Triggers Acetylcholine release
- Acetylcholine diffuses across synaptic cleft
- Binds to acetylcholine nicotinic receptors
- Opens ligand-gated Na+/K+ channels
- Evokes very large graded end plate potential
- Depolarises adjacent membrane (bottom of sarcolemma folds) to threshold
- Opens voltage-gated sodium channels to evoke new AP
- Acetylcholinesterase removes Acetylcholine
Describe the ultrastructure of CNS synapses.
- Range of neurotransmitters
- Range of post-synaptic potentials
- Anatomical arrangement
- Synaptic connectivity
Describe the range of postsynaptic potentials in the CNS.
- Fast EPSPs (ionotropic)
- Slow EPSPs (metabotropic)
- Fast IPSPs
- Slow IPSPs
What postsynaptic potential is found in the NMJ?
Only a large endplate potential.
Describe the anatomical arrangement of the CNS and NMJ.
NMJ - doesn’t change
CNS - axo-somatic, axo-dendritic and axo-axonal
Describe synaptic connectivity.
Convergence or Divergence
Describe the process of synaptic transmission in the CNS.
Similar to NMJ however, MORE VARIABLE an HARDER TO PREDICT (due to the range of ultrastructures that exist).
What is created at location where AP releases transmitter which activate receptors on a second cell and opens ion channels?
A graded potential.
When a synapse is closer to the axon hillock, what is the result?
A more effective depolarisation and hyperpolarisation.
What is an EPSP?
Excitatory post-synaptic potential (make cell fire, excitatory, towards threshold, graded)
What is an IPSP?
Inhibitory post-synaptic potential (stop reaching threshold, less likely to fire, inhibitory, graded)
What channels are opened with an EPSP?
Na+/K+ channels or closing K+ G-protein channels
Give an example of an EPSP neurotransmitter.
Glutamate
What channels are opened with an IPSP?
Cl- or K+ channels, G-protein
Give an example of an IPSP neurotransmitter.
GABA
What is signal transduction in neurons?
Movement of electrical potentials through afferent neurons in PNS to interneurons in CNS na then to efferent neurons in PNS with the use of different neurotransmitters.
Describe the properties of a graded potential.
- Decremental
- Non-propogated
- local potential (graded)
- can summate (therefore important in synaptic integration)
What decides when an action potential should be fired?
The graded potential.
What is the resting membrane potential generated by?
The permeability of the resting membrane to K+.
List examples of graded potentials.
End-plate potential, EPSP, IPSP, pacemaker potential
Is the end plate potential always large enough to evoke an action potential?
Yes. The end-plate potential has a large safety factor and in a healthy person always exceed threshold. Like all postsynaptic potentials, it is a graded potential (albeit a very large one) and is therefore not all or none. It is evoked in the end-plate (ie the postsynaptic side of the synapse) and not in the motoneurone terminal (which is the presynaptic side).
What is neostigmine?
An anticholinesterase and therefore potentiates transmission at the NMJ
What is the mechanism of action of helicholoium?
Prevents choline uptake
What is the mechanism of action of hexamethonium?
Blocks transmission at autonomic ganglia.
How does saxitocin (shellfish poisoning similar to tetrodotoxin) act at the NMJ?
Block the opening of voltage-gated Na+ channels in and all-or-none fashion.
How does the lethal injection work?
100mM K+ (normally intracellular K+ = 150mM and extracellular = 5mM) therefore increasing extracellular K+ decreases concentration gradient and RMP depolarising cell. Severe cardiac effects result (increased/ uncoordinated AP firing initially and then ion channels left in inactivated state).
At the NMJ, is the end-plate potential always big enough to reach threshold and fire an AP?
Yes. Also, only inhibits a depolarising potential unlike the CNS.
At the synapses of the CNS, is the end-plate potential always big enough to reach threshold and fire an AP?
No. Individual postsynaptic potentials are typically very small and must summate with each other to reach threshold. Synapses in the central nervous system also have the added complexity of inhibitory postsynaptic potentials.
What is Myasthenia Gravis?
The autoimmune destruction of nicotinic cholinergic receptors at the NMJ meaning that the end-plate potential is smaller and the “safety factor” is reduced.
What does repetitive stimulation of a nerve cause?
Evokes a progressively smaller end-plate potential.
What is the role of anticholinesterase?
Inhibits breakdown of acetylcholine in the synaptic cleft by acetylcholinesterase and therefore, increases the concentration of acetylcholine available to activate the muscle.
What is botulinum toxin?
Neurotoxic protein produced by bacterium clostridium botulinum, prevents the release of acetylcholine at NMJ.
What is hexamethonium?
Nicotinic receptor antagonist located only in autonomic ganglia only.
What is Hemicholinum?
Blocks re-uptake of choline transported at the presynapse, indirect acetylcholine antagonist.
What is d-tubocurarine?
Toxic alkaloid, nicotinic receptor antagonist.
What is succinylcholine?
Binds to nicotinic acetylcholine receptor, longer duration of effect than acetylcholine, maintains membrane potential above threshold and doesn’t allow muscle to repolarise. When acetylcholine bonds, it cannot cause further depolarisation. Calcium still removed from cytoplasm and taken up by SR so results in flaccidity.
