Mechanosensory

Question 1

How is the ion channels in mechanosensing gated?

Answer 1

By physical disturbance (stretch sensitive)

Question 2

What is the purpose of a statocyst?

Answer 2

Sensing gravity

Question 3

What is the function of the heavy crystal in the statocyst?

Answer 3

Higher density –> pulled towards the epithelium and is sensed by the cilia.

Question 4

True or false: Mechanosensing is most often mediated by hair-like structures.

Answer 4

True.

Question 5

What are the two types of hearing?

Answer 5

Particle motion and pressure waves

Question 6

Descripe particle motion

Answer 6

Low sensitivity, short range, directional, only low frequencies

Question 7

Descripe pressure waves

Answer 7

Most common, very sensitive, long range, non-directional, broad frequency span

Question 8

How is direction perceived in pressure wave hearing?

Answer 8

Two ears –> time difference and intensity difference

Question 9

What is the minimum distance between the two ears to be able to perceive direction?

Answer 9

There should be at least 1 ms delay, corresponding to 3 mm

Question 10

Describe the general structure of vertebrate ears

Answer 10

The pinna (outer ear) is the directional filter, the tympanic membrane sense the pressure difference by vibrating, the columella/ossicles transmit and amplifies/dampens vibrations, the vibrations are transmitted to fluid filled cochlea through the oval window, and travels through the vestibular canal to the tympanic canal, and finally the basilar membrane vibrates and stimulates the receptor cells (hair cells)

Question 11

What are the properties of the cochlear?

Answer 11

The basilar membrane changes along the length of cochlear. Specific areas vibrates most with specific frequencies (tones), highest frequencies in the first part, vice versa.

Question 12

Describe the receptor cells in vertebrate hearing.

Answer 12

Several stereovili and cilia forming collar. The cilia and villi are connected by tip links. Vibrations cause stereovilli/cilia to move relative to each other. The tip link directly pulls open stretch sensitive ion channels

Question 13

What are the pros/cons of echolocation?

Answer 13

Cons: It’s energetic expensive, it can allow eavesdropping
Pros: it allows for more information, and hunting in the dark

Question 14

Describe the sound making of dolphins.

Answer 14

Sounds are produced by vibrating air sacs, and are focused by fat body (aka melon)

Question 15

Describe the sound hearing of dolphins.

Answer 15

Incomming sounds (echo) picked ud by oilfilled lower jaw and transmitted to auditory bullae (= inner ear)

Question 16

Moths can “eavesdrop” on bats. Describe what the A- and B-cells facilitate.

Answer 16

A-cells: low threshold –> alert
B-cells: high threshold (the bat is within 0.5 m) –> wings collapse, moth drops.

Question 17

How can you predict and experimentally confirm the membrane topology and subunit composition of an ion channel?

Answer 17

Membrane topology: You make a plot of the hydrophilic and hydrophobic areas of the protein sequence (hydropathy plot, 20-25 AAs needed to cross the membrane)
Subunit: crosslinking + western blot. Protein crystals (x-ray crystallography) –> 3D structures.

Question 18

Which methods can be used to test the selectivity, conductivity and gating mechanism of ion channels?

Answer 18

Electrophysiology.

Question 19

Nociception (sensing pain) can be subdivided into thermosensation, chemosensation and mechanosensation. What are the molecular differences? Give some examples for ion channels belonging to each of the three categories. Explain their membrane topology, channel subunit composition, ion selectivity and gating mechanism.

Answer 19

Thermosensation: gated temperature changes, TRPV1 (sensing capsaicin and > 42 C) - micromovements in any direction
Chemosensation: gated by a chemical ligand TRPM8 (sensing methol), GPCR
Mechanosensation: mechanically gated by either forces from lipids, or forces from filaments: SWELL1 (osmoregulation in vertebrates)

Question 20

Which proteins from hair cells do you know are involved in hearing? How are these transduction channels gated? What happens after channel opening?

Answer 20

TMC1 (TM channel 1), TMHS (Tetraspan Membrane Hair cell Stereocilia), TMIE (TM inner ear), all are channel forming proteins
Mechanically gated by tip link (cadherin-like proteins) when stereovilli is stimulated by vibrations.
Cation influx –> depolarization (voltage gated ion channels (Na+ and K+)) –> action potential is generated.

Question 21

What is proprioception? Which structures and channels are involved?

Answer 21

Sensing where your body parts are in space. Piezo receptors, muscle spindels, golgi tendon organs, joint receptors

Question 22

Peripheral baroreception is a combination of chemo- and mechanosensation. Which channel types are involved and how is their subunit composition?

Answer 22

ASIC2 subunit is mechanically gated, ASIC1 is chemically gated (H^+ sensing), ASIC3 (H+ sensing)
Topology: trimeric (function defined by subunit composition), 2 TMDs (like a fist)

Question 23

Give examples for mechanically activated channels involved in osmoregulation in bacteria and
mammals.

Answer 23

Bacteria: MscS and MscL
Mammals: SWELL1 and LRRc8

Question 24

Mechanically activated ion channels can be gated by forces from the membrane (stretching,
shrinking, bending) or from filaments tethered to extracellular or intracellular parts of the channels.
Give examples for each of these mechanisms.

Answer 24

Forces from filament: receptors involved in hearing (tip-link)
Forces from lipid: Piezo receptors

Question 25

What kind of sensing are the free nerve endings on the skin responsible for?

Answer 25

Pain and temperature

Question 26

What structures are responsible for sensing touch?

Answer 26

Merkel’s disc, Meissner’s corpuscle and hair follicle receptors

Question 27

What kind of sensing are the pacinian (or lamellated) corpuscle responsible for?

Answer 27

Vibration and pressure

Question 28

What kind of sensing are the Ruffini’s endings responsible for?

Answer 28

Stretch

Question 29

Are the nocireceptors and thermonreceptors in the free nerve endings in the skin low treshold or high treshold receptors?

Answer 29

High treshold

Question 30

Are the merkel cell receptors and meisner corpuscle receptors low treshold or high treshold receptors?

Answer 30

Low treshold

Question 31

Describe the general root in the PNS for afferent noci-, mechano and proprioceptors.

Answer 31

The primary afferent neuron go through the dorsal root ganglion (cell body) –> dorsal horn (synapses) innervating secondary afferent CNS neurons –> CNS neurons go through the spino-thalamic tract –> spine –> thalamus

Question 32

The proprioceptors also have an alternative root, describe this.

Answer 32

Afferent cells through dorsal horn, connected to efferent motorneurons by interneurons in the dorsal horn –> efferent motorneurons through ventral horn –> periphery. This allows for a quicker response

Question 33

How does hard texture food influence food choise in flies?

Answer 33

Mechano neurons sense hard texture –> GABA inhibits gustatory response for sweetness –> finds another food, that is soft

Question 34

Describe the parallel sensory system in C. elegance of food removal.

Answer 34

Food deprivation triggers a glutamate response in both chemosensory neurons and mechanosensory neurons, leading to food foraging behaviour. Both of these systems needs to be knocked out before foraging behaviour disappears (they can compensate with either).

Question 35

Describe the sex specific courtship behaviours of flies.

Answer 35

Females: pulse song induces reduced locomotion (allowing males to come closer) –> increased receptivity to mating
Males: pulse song induce both increased locomotion and exploratory courtship activity directed towards nearby flies

Question 36

Which neuron are thought to be responsible for the male specific courtship behaviour and are lacking in female flies?

Answer 36

pC1

Question 37

How is the somatic sensory system impacted by autism spectrum disorder?

Answer 37

The mechanosensors sensing tactile stimuli holds a lower threshold –> hypersensitive to touch

Question 38

How did deletion of the mecp2 gene during development in mice impact their social behaviours as adults?

Answer 38

Lead to deficits in social behaviour and showed higher levels of anxiety

Question 39

How was piezo identified?

Answer 39

They found a specific cell type when stimulating it signaled an electrical response.
How did they found this: They knocked down many genes. Until they found a knocked down gene that when knocked down made the cell no longer intracellular signaling.

Question 40

Which strategy was used to determine the structure of Piezo?

Answer 40

cryo-electron microscopy (cryo-EM), scientists have made progress in unravelling the Piezo channels’ bizarre, three-bladed structure, but a complete mechanism has been elusive. The exact structure has not been found within the cell, only extracellular.

Question 41

How was the physiological function of Piezo2 unravelled?

Answer 41

There was a hint from a doctor with two female patients. They could se their body but when blindfolded they had no idea where their bodyparts were in the room (where placed compared to their body.)

Question 42

How do single versus groups of flies respond to the odour of CO2?

Answer 42

To their surprise, they found that solitary flies only weakly avoid CO2, and that only a group of flies strongly avoid the CO2.

Question 43

What is the sensory input that enhances the aversion to CO2 in groups of flies?

Answer 43

The sense of touch:
The encounter response: when a fly walked away from CO2 and met another fly, the fly they encountered would touch the first fly and through mechanical touch. The mechanosensory channel NOMPC is important for this.