Lecture 5 - Transduction At Nerve Endings Flashcards
Why is a nematode worm tethered?
So a mechanical probe can meet the nematode worm
What are C.elegans?
Transgenic that expresses a yellow fluorescent protein
What happens when the mechanical probe is applied?
It gives rise to mechanical stimulus on the worm
What is the ratio fluorescence indictive of?
What the calcium concentration there is in the neuron
What is role of mechanical stimuli?
Activating ion channels in the membrane that allows calcium across neuron membrane
What do humans have?
Homologous proteins
Genes that show substantial homologous with the genes in the c.elegans
What are mammalian equivalent of MEC4 and MEC2?
ASIC channels
Where are ASIC channels expressed?
Pain sensing neurons
What are the sensory modalities?
Vision Hearing/balance I.e. mechanoreceptors Taste I.e. chemoreception Olfaction I.e. chemoreception Skin and other body surfaces
What are examples of other body surfaces?
Light touch Vibration Warm/hot/cool/cold I.e. thermoreception High-threshold mechanoreceptors/pain Chemoreception/Pain
What are other sensory modalities?
High threshold mechanoreception in viscera (respond to distension)
Chemoreception in viscera (pain)
Chemoreception in circulation/brain e.g. carotid body, medulla surface
Proprioceptive input (mechanoreception) - muscle length/position/tension - tendon stretch
What are the elements required to transduce the world into nerve impulses?
- Light sensitivity
- Chemical sensitivity
- Mechanosensitivity
- Temperature sensitivity
Light sensitivity
Rods
Cones
Blue light sensitivity RGC
Chemical sensitivity
Odorant receptors
Taste
Pain
Mechanosensitivity
Touch
Pain
Joint position
Temperature sensitivity
Skin thermosensitivity
Pain
Where is the pacinian Corpuscle found?
Skin/membrane
Inside our abdomen
Myelinated axon
Signalling mechanical stimuli
What are the features of Pacinian Corpuscle?
lamellated
Fluid filled capsule
Expanded myelin
What is found inside the Pacinian Corpuscle?
Stretch of unmyelinated axon
What happens further along the nerve?
Myelination begins as the nerve fibre is coming towards the edge of lamellated structure
What is found outside the nerve fibre as it’s going towards the central nervous system?
Myelin
What is Crystal and probe?
A device that can change an electrical stimulus into a motion
What occurs when the crystal is activated?
Mechanical device can be used to press down on the Corpuscle
What is the role of micro-manipulator?
Holds the Corpuscle in position
Inactivate the first node of Ranvier by applying circumscribed pressure to damage the nerve and prevent it from signalling by applying pressure to the first node
How were recordings made?
Ex vivo preparation from isolated Pacinian Corpuscle
What is rectangular displacement?
Shows when the pressure is applied to the Corpuscle
How can the potential difference be recorded?
Extracellularly because of the incorporation of oil into the preparation
What does the use of oil prevent?
Miniature ex vivo preparation from drying out
When a generator potential is seen?
When a maintained pressure is applied onto Corpuscle
What is a biological device very sensitive to?
Changes in pressure
Not sensitive to maintained pressure
What properties does the capsule have?
Very special visco elastic properties
What is Pacinian Corpuscle?
Vibration sensitive device
What is a decapsulated preparation?
Stripped off the lamellated structure over the Corpuscle
How do you achieve a prolonged response?
Change the properties of receptor
Take capsule off
What are the steps for a propagated action potential?
Stimulus (e.g. mechanical) Transduction Generator potential Activation of the first node Propagated action potential
What happens when a large current is applied?
can only recruit one AP
What happens when a long depolarising stimulus is applied?
The node is only generating a single action potential
What limits the response to one or two action potentials?
Adaption to the stimulus
What happens when long lasting currents applied to myelinated axons?
2 action potentials is achieved
What blocks K+ channels?
Tetroethanol amino ions
What is expressed at the node of Ranvier?
KV7
What is KV7?
Kinetically slow K+ channel
What is the result of application of TEA?
Convert accommodative nerve into a nerve that does not accommodate (continuously generate action potential)
What is accommodation?
Allows nerve to soak up excitatory stimuli
Nerve is not continuously excited
What are different categories ion channels expressed by sensory neurons ?
- Voltage-gated
- Ligand-gated
- Temperature-gated
- Mechanically-gated
Voltage-gated
Activation depends on changes in membrane potential [Nav channels]
Ligand-gated
Activation depends on binding of a chemical
Temperature-gated
Activation depends on fall or an increase in temperature
Mechanically-gated
Activation depends on membrane stretch
What can be done to cell bodies of small diameter axons?
Dissociated and maintained in culture
What underlies induction and propagation of action potentials?
Na+ channels
What is a stimulating probe?
A device that converts changes in electrical probe potential into mechanical movements
What can be seen in phase contrast?
Nucleus
Nucleolus of neuron
What does a sensory neuron have?
Sensory nerve ending in the body
What is low threshold mechanoreceptors?
Expressing channel that require less membrane stretch to get them to open
What does MEC channels get?
Mechanically-gated currents
What does membrane stretch do?
Activate channels that can generate an inward current which depolarise the neurons
What are TRP channel?
Transient receptor potential
Prototype is deficient in a Drosophila mutant
TRP channels
Group of ion channels located mostly on the plasma membrane of animal cell types
What does TRP channels mediate?
Variety of sensations
Pain, hotness, warmth, coldness
Different kind of tastes, pressure and vision
How are some TRP channels activated?
Molecules found in spices like garlic, chilli pepper, wasabi
Others by: menthol, camphor, peppermint and cooling agents
What do some TRP channels act?
Sensors of osmotic pressure, volume, stretch and vibration
How are sensation of warmth brought about?
Interaction between keratinocytes in skin which releases ATP and ATP receptor sensory nerves (TRPV4 + TRPV3)
What an TRPV2 be gated by?
Noxious heat (temperature above 43)
What do TRP channels form?
homo/heteromultimers
Polypeptide crosses the membrane 6 times
Hairpin loop - lining the channel pore
What is TRPA1?
Sensitive to cold temperature (-10) + variety of chemical stimulators
Garlic, cinnamon, noxious cold receptors
Where is TRPM8 present?
Skin and mouth and tongues and lips
Gated by cool temperatures
What is microneography?
Recording of the activity of single afferent in a mixed nerve in human
Use sharp microelectrode and carefully position within a human peripheral nerve
Damage some of the axons in nerve
What is a Peltier device?
Convert electrical signal (current) into a movement of heat
Creates a Temperature difference by transferring what between 2 electrical junctions
What does Menthol potentiate?
Cool responses known to be due to activation of TRPM8
Where is TRPV1 expressed?
small diameter neurons
What is in-Situ hybridisation?
mRNA is being expressed for TRPV1 in small diameter sensory neurons in DRG
What is Hyperalgesia?
Changes in membrane properties of a primary sensory neuron leading to an increase in responsivensss (hypersensitivity)