Cochlear Physiology ll: Hair Cell Functions Flashcards
Anatomy Homeostasis Metabolism of both fluids EP generation and maintenance Recycling-gap junction Genetic hearing loss with Cx mutation
What force BM causes on the hair cells?
BM vibration to shearing or bending
What happens to channels with bending of stereocilia?
Bending of stereocilia to open ion channels
What response is the current from HC?
AC vs DC response
What is the linearity of Stimulation of HC and Cochlear Transduction?
Nonlinearity
What can we say about the indent connection of the tectorial membrane and IHC?
The tectorial membrane above IHCs does not show such indents. Therefore, it is concluded that the stereocilia of IHCs does not physically connected with tectorial membrane.
What causes IHC bending?
Hair bundles on IHCs are not embedded in TM
Bending is driven by Hensen’s strip and hydraulic force
Which types of stereocilia are on the left and right?
Stereocilia on OHC (left) and IHC (right)
Which types of links are on the OHC stereocilia? (3)
1) Row-to-row
2) Side-to-side
3) Tip-to-side (tiplink)
Which links are thicker across the stereocilia on OHC?
Row to row and side to side are thicker, they hold the stereocilia together
What do tip-to-side links do?
Control MET Channels
What is the connection between hydraulic force, IHC, and the row/side links?
The stereocilia on IHC are driven by the hydraulic force, there are no strong row/side links
The lack of strong links across the stereocilia makes them easier to bend in response to hydraulic turbulence.
What is the battery theory?
The cochlea produces an electric field potential essential for hair cell transduction and hearing. This biological “battery” is situated in the lateral wall of the cochlea and contains molecular machinery that secretes and recycles K+ ions.
What occurs in the image?
Standing current: current when there is no stimulation
Describe the Transduction channels: (3)
Location: inside the stereocilia
Not ion selective
The gates are controlled by tip links
What is occurring in this picture?
What is occurring in this image?
The entrance of MET channels are likely located at the root of tiplink on the shorter stereocilia.
What are tip links made of?
CDH23 and PCDH15 comprise tip link, which inserts into the stereocilia membrane at the tip densities.
Tip densities contain scaffolding proteins, which bind to the cytoplasmic domain CDH23 and PCDH15 and anchor the tip link.
Several myosins have been localized to the tip density region and proposed to participate in MET adaptation, stereocilia actin dynamics, localization of lateral links, and cargo transport.
Tension on the tip link gates the MET channel.
What are the ion channels involved in HC functions?
K+, C Ach MET ions channels
What is the sequence of events in hair cells in response to sound?
- Deflection—transduction channel opening, IT increase
- K inward—depolarization
- ICa increase causes:
- IK increase—repolarization
- Neurotransmitter release
- AP of auditory N
When a hair cell depolarizes, voltage-gated calcium channels at the base of the cell open, and the resulting influx of calcium causes synaptic vesicles to fuse to the cell membrane and to release a neurotransmitter into the synaptic cleft between the hair cell and the cochlear nerve fibers
IT: transduction current
What occurs to the standing current when there is no deflection of hair cells?
Standing current balanced by outward current—resting potential
Towards where does the deflection occur on hair cells and what happens next?
Deflection towards kinocilium (laterally in cochlea) increases inward current -> depolarization and cause 8th firing
What direction of deflection of Hair cells cause hyperpolarization?
Deflection towards modiolus (medially), decreases inward current (hyperpolarization)
What is cochlear microphonics?
Receptor potentials in the cochlea that mimics sinusoid stimulation (sound)
In cochlear microphonics, which type of current is it?
Receptor Potential
Which current components does the cochlear microphonics contain?
Contain DC and AC components
Which of the two components copies the stimuli in cochlear microphonics?
AC component follows (copies) stimuli
What can we say about the symmetry in cochlear microphonics?
Asymmetrical at higher frequency: due to accumulation of K, related to SP.
What is the impact of frequency on receptor potential? (AC component)
The AC component amplitude is decreased with increasing frequency:
- Due to the capacitance and resistance of the membrane: the low-pass feature
- Due to the low-pass feature of the recording electrode
- Impacts OHC motility how?
What is the impact of frequency on receptor potential? (DC component)
The DC component amplitude is increased with frequency
- During the stimulation, K is accumulated inside HCs,
- This is more significant when signal frequency is high, due to lack of time to remove K.
Explain the non-linearity of the Cochlear microphonics in response to sound level:
Non-linear means that while the intensity level (the stimulus dB) is increased, the CM amplitude also increases BUT it does reach a point where it will not increase and eventually at higher intensity levels will “roll-over” which means the amplitude of the CM will decrease at those levels
In what ways is the cochlear nonlinearity shown? (2)
Response-Level function
Distortion Products in OAE (F1 and F2)
Where does the cochlear nonlinearity originates from?
Inside the cochlea
What does Cochlear Microphonics nonlinearity depend on?
Active mechanism of intact OHC
What is the CM nonlinearity vulnerable to?
Vulnerable to damaging factors
What occurs in this graph related to OHC and cochlear nonlinearity?
- The electrical response is compressed as seen in CM O/I function, which is associated with gain reduction with SPL
- MET channels is controlled by Ca2+
- Much stronger compression in active gain
- Not fully understood
Where does the nonlinearity occurs shown in this graph? (2)
Nonlinearity occurs in a restricted area around CF, where a rapid increase was seen at low-moderate intensity; saturated at a high level.
Linear growth at frequency away from CF
Explain the feature of OHC amplification (3):
1) It is frequency selective
2) Level selective (highly compressive)
3) OHC as amplifier for stimulation to IHCs in response to depolarization
Solid line: BM response at 10 kHz region by 10 k stimuli, compressive
Dashed line: at 10 kHz region by 5 k stimuli, linear
The diff shows active gain
What does this image show? (3)
From OHC motility
Provides sharp tuning (?)
Provides high sensitivity
What occurs to low sound BM vibrations levels by OHC?
The active components by OHC increase the sensitivity and tuning
What are the locations of the vibration measurement on the organ of corti? (2)
BM and RL
What do we consider the difference in amplitude between the BM and RL?
The difference in amplitude between BM and RL can be considered as the gain by OHCs, which is larger at low sound level.
At which sound level is the gain of OHC larger?
Larger at low sound level
Explain the cochlear tuning: (5)
- The Sharp tuning is seen in receptor potential, BM vibration and auditory nerve
- The second filter is not needed
- Active mechanism and sharp tuning
- OHC motility contributes to sharp tuning
- However, the exact mechanism is not clear, OHC motility is not tuned in isolated OHCs
The sharp tuning and nonlinearity depends on:
OHC
What can we say about the fact of the results of OHC as motors? (4)
Dallas vs. Brownell vs. Many researchers
- Dallas: OHC lesions elevate threshold
- Brownell: OHCs motion in response to voltage changes
- Many researchers: OHC motility contributes to cochlear amplifier
- Receptor potential activates motors
What the THREE types of motility of OHC?
Fast motility of OHC bodies
Slow motility of OHC bodies -> K+, Ca++ and ATP
Motility of hair bundles
What are the general features of fast motility of OHC body? (4)
- It follows the hearing frequency range
- It is different from muscles: independent of ATP and Ca++, does not require muscular proteins (actin and myosin)
- Driven by voltage difference across the cell membrane
- Asymmetric length change up to 5%, without volume change
What are the methods for recording fast motility? (2)
a: Whole patch
b: Microchamber
What can we see from this picture related to the asymmetric length change?
The length shortening is not saturated with depolarization.
What causes the fast motility of OHC?
Prestin protein in plasma membrane rich in OHC but not in IHC
What is the gene isolated to identify prestin?
SLC26A5
Where is prestin located in OHC and when does it appear?
lateral wall of OHC and Prestin appears at the same time as OHC motility after birth
What can we see from this picture (especially in b)?
In b, the motility can be seen in cells expressing prestin and in d, we can see the motility following frequency of stimulation
What are the characteristics of Fast OHC motility? (3)
- Proportional to MP (membrane potential) changes
- Fast: flows up to 20 kHz
- Length change up to 5%– 1-5 micrometer, comparable to BM vibration by sound
How does OHC motility enhance stimulation to IHCs? (4)
- Not clear
- Could be by hydraulic turbulence
- Could be by By changing the interaction from the tectorial membrane? (Shortening of OHC length may pull the tectorial membrane closer to the reticular lamina)
- No methodology can ensure a reliable observation in this small area.
How does OHC length change impact coupling to IHCs?
OHC shortening reduces the distance between IHC and TM
What is the relationship between shearing of TM and RL and OHC motility?
The shearing between TM and RL and fluid flow are enhanced by OHC motility to stimulate IHCs
What do we need to know about prestin?
Gene structure: not only the coding sequence, but also regulating zones
Gene location on chromosome
AA sequence and 3-D/4-D structure of prestin
Evolutional changes of prestin, AA for high Fre.
How prestin responds to voltage
Pathological changes
Quantity changes
Functional change?
Does the motility of OHCs saturate with increasing sound level?
No
How is the cochlear amplification/motility tuned? (3)
- Electrical resonance of HC (not in mammal
- Mechanical resonance of BM
- Tonotopic differences in the stiffness of hair bundles.
Explain the electrical tuning:
HCs in amphibians, reptiles and birds are tuned (electrically), not seen in OHCs of mammals.
What can we say about the motility of hair bundles seen in studies on a turtle? (3)
The electrical resonance in turtle HCs shows best frequency (turned)
The oscillation following membrane potential
The electrical resonance may drive hair bundle to move (Fettiplce 2006)
What can we say about the mechanism for amplification tuning in mammals? (3)
- OHC motility is not sharply tuned
- The sharp tuning of BM by OHCs is not fully understood.
- “initiated” from BM passive tuning
- From hair bundle motility?
- Hair bundle motility is seen in amphibians, not in mammals
What is the new evidence for hair bundle motility in mammalian cochlea?
In mammals, stiffness changes with deflection
More recently, the length change
What is the difference in the dynamic range of the CM compared to the typical range of the auditory nerve?
The dynamic range for CM is larger than that of typical range for auditory nerve
At which level is cochlear compression established?
the cochlear compression is not fully established at CM level but at the active feedback from OHCs to IHCs.
