Mechanotransduction

Question 1

Middle ear

Answer 1

• ossicles: malleas, incus, and stapes are the smallest bones in the body
• muscles: dampen the vibration of ossicles during loud noises, speech, and chewing

Question 2

Physical amplification in middle ear

Answer 2

• ossicles concentrate the vibration on a smaller surface area which increases the pressure per unit area by 17x
• ossicles also act as levers (amplify by 1.3X

Question 3

Inner ear

Answer 3

• longitudinal waves in the air make the oval window move in and out
• causes transverse waves in basilar membrane
• a particular region of the basilar membrane flexes back and forth in response to sound of a particular frequency

Question 4

Von bekesy: physics of the basilar membrane

Answer 4

• base: narrow and stuff - vibrated to high frequncies

- apex: wide and floppy - vibrates to low frequencies

Question 5

Hair cells

Answer 5

• cells where transduction occurs
• different hair cells maximally activated by different frequencies)
• stereocilia on hair cells deflected by tectorial membrane
• kinocilium thought to direct growth of stereocilia along a uniform axis
  
  • if kinocilium is absent, stereocilia can form facing the wrong direction or may not be polarized
  • in some species the kinocilium retracts later in development

Question 6

Tip links and hcMET channels

Answer 6

• tip links: (cadherin 23 or protocadherin 15)
  
  • connect stereocilia to eachother
  • upon cilia deflection, change in tension on hair cell hcMET channels (hair cell mechanoelectrical transduction)

Question 7

Transduction in hair cells

Answer 7

• ultra low latency depolarization upon hair cell deflection
• at rest, hcMET gates are partially open
• deflection of cilia toward long side open hcMET
• deflection of cilia toward short side closes hcMET
• K+ and Ca2+ enter hair cells through hcMET causing depolarization
• to pure tones (sine waves)<3000Hz, hair cells oscillate between depolarization and hyperpolarization (AC)
  
  • another source of frequency information
• at higher frequencies (>3000Hz) oscillations blue together into depolarization (DC)

Question 8

K+ flow in hair cells

Answer 8

• fast cycling between depolarization and hyperpolarization led to specialization in hair cells
• K+ mediate both hyperpolarization and depolarization
• hair cells K+ gradient mostly maintained by passive ion flow
• accomplished by having 2 different extracellular environments for different parts of the hair cell
• scala media: filled with endolymph (K+ rich/Na+ poor)
• reticular lamina: tight junctions - no ion exchange
• basal part of hair cells: bathed in perilymph (Na+ rich/K+ poor)

-stria vascularis enriches scala media with K+

Question 9

Division of labor in cochlea

Answer 9

• inner hair cells carry sound information
• outer hair cells provide cochlear amplifier
  
  • deflection of the cilia + central feedback
    
    • upon depolarization, Prestin unbinds Cl- and contracts
  • sharpen and amplify basilar membrane oscillations

Question 10

Vestibular hair cells

Answer 10

• hair cells located in macula of saccule and utricle, and ampullae of semicircular canals
• works same way as hair cells in cochlea but mature vestibular hair cells still have kinocilium

Question 11

-otolith organs

Answer 11

• heavy otoconia resting on squishy otolithic membrane - shear and sway
• gravity causes membrane to shift relative to hair cells in macula
• oriented hair cells:
  
  1. Utricle: senses translation in horizontal place and sideways head tilts
  2. Saccule: senses translation in vertical plane and up/down head tilts

Question 12

Semicircular canals

Answer 12

• inertia causes endolymph lag behind head movement

- causes distortion of floppy cupula and displacement of embedded hair cell cilia

Question 13

Somatosensory afferents

Answer 13

• cell bodies located in dorsal root ganglia
  
  • long afferent fibres transit information from the skin to spinal chord
  • called pseudounipolar: AP propagation need not pass through soma
• receptor endings of mechanoreceptors often surrounded by specialized structures

Question 14

Mechanotransduction of touch

Answer 14

• stretching/deformation of membrane allows actions to enter a depolarize the afferent fibre
• many mechanoreceptors thought to express piezo2 channels (pressure channels)

Question 15

Function of touch receptors

Answer 15

• each type of touch receptor has evolved to detect some behaviourally relevant touch stimulus
• response properties of each receptor are dictated by
  
  • physical structure of receptor ending
  • ion channels on unmyelinated ends of afferent fibres
  • location of receptor

Question 16

Merkel receptors

Answer 16

• continuous (slow adapting) response
• slow pushing response
• perceives fine details
• shallow location (tips of primary epidermal ridges)
• small (2-5mm)

Question 17

Meissner receptors

Answer 17

• respond to change (rapid adapting response)
• perceives flutter, micro slip, hand-grip control
• shallow location (tips of dermal papillae)
• small (3-5mm)

Question 18

Ruffini receptors

Answer 18

• continuous (slow adapting) response
• perceives stretching
• deep location (mid dermis)
• large (10-30mm)

Question 19

Pacinian receptors

Answer 19

• response to change (rapid adapting response)
• rapid vibration of upper range
• perceives vibration and texture by moving fingers
• located deep (subcutaneous fat)
• large (entire finger or whole hand)

Question 20

Mechanoreceptors for propioception 1.

Answer 20

• muscle spindles:
  
  • sensory fibres coiled around intrafusal muscle fibres sheathed in connective tissue (tension distorts afferent endings to activate mechanoreceptors)
  • group 1a: rapidly adapting, and give info about limb movement
  • group 2: sustained responses, static limb position
• Y (gamma) neurons: cause intrafusal muscle fibres to contract
  
  • adjust tension and sensitivity of spindle sensor
• Golgi tendon organ:
  
  • group 1b sensory afferent woven throughout the collagen fibres that form tendons
  • tension distorts afferent ending to activate mechanoreceptors

Question 21

Pain

Answer 21

• AB fibres that conduct touch info are not involved in pain transmission
• responses to mechanical or thermal stimuli saturate in the range where stimuli would be perceived as painful
  
  • nociceptors being to activate in this painful range

Question 22

Nociceptive ion channels

Answer 22

• variety of painful stimuli (mechanical, thermal, chemical)
• nociceptive fibres lack the specialized endings like touch receptors
• called free nerve endings (unmyelinated)
• express various ion channels sensitive to painful stimuli
• many free nerve endings act as polymodal nociceptors (responsive to several types of painful stimuli)

Question 23

Transient Receptor potential Channels

Answer 23

• TRP channels comprise a large family of cation channels that are activated by painful stimuli
• 4 subunits with 6 Transmembrane domains each

-free nerve endings that act as a polymodal nociceptors presumably express multiple types of TRP channels to detect various form of painful stimuli

• TRPM8 detects cold and menthol
• TRPV1 detects heat and capsaicin