Active (micro) mechanics and signal transduction Flashcards
OHC Mechanics / Hair Cell Signal Transduction / Neuron Action Potentials
Review of macromechanics: What did Selleck’s studies show us?
resolving power of fine tuning of the BM
Review of macromechanics: What are the sources of non-linearity?
system amplifies low level stimuli; doesnt do this with high level stimuli
OHCs are thought of as _________________ driven by a physiological motor
mechanical vibrator
Electrical stimulation of hair cells showed that they were capable of _________ in response to a depolarizing stimulus and _________ in response to a hyperpolarizing stimulus
contracting; elongating
depolarize makes the cells _________
shorter
hyperpolarize makes the cells _________
taller
OHCs help explain the resolving power in the cochlea and how it distinguishes between ____ Hz to _____ Hz
1000 Hz to 1001 Hz
what are the obvious possible source of OHC
Olivocochlear bundles (OCB)
diagram: source of OHC control
how would it work? think about __________
waves
when the two waves are perfectly in phase with one another, their signals _______ each other
augment; add
when the two waves are slightly out of phase with one another, the overall signal is _________ (results in ___________ interference)
dimished; destructive interference
when the phase shift between them reach 180 degrees, the two waves _________ each other
cancel
the result of this type of motion is a ___________
resonance
resonance can facilitate vibration of the BM, enhancing _________ at a specific location along the BM
frequency selectivity
resonance ________ desired vibration and will actually _________, by cancellation, the vibration of the adjacent areas of the BM
amplifies; reduce
OHC exhibit a gradient in high from base to apex: ________ um tall at the base and _________ um tall at the apex
<15 um and >90 um
OHC ______ when hyperpolarized and ____________ when depolarized
elongate; shorten
the lateral wall of OHC is specialized as a _____________ structure
trilaminate structure
what does the trilaminate structure consist of?
1) wrinkled plasma membrane (outermost)
2) subsurface cisternae (innermost, ER like)
3) intervening extra-cisternal space
radially orientally pillars connect the plasma membrane to a cortical _________ network
actin network
what is actin network arranged as and what is it cross-linked by
arranged as circumferentially orientated parallel fibers and cross linked by spectrin; creating flexible scaffolding
diagram of OHC with lateral wall components
The ________ is found within the lateral wall plasma of OHC
motor
_________ likely serves as the motor
Prestin
What is Prestin found to convey?
electromotility to transfected cells
why is Prestin unique? list 2 reasons
1) does not require ATP hydrolysis for energy
- directly on membrane potential
- uses electrical energy directly
2) does not require Ca 2+ for activation
Prestin works _________ than any other biological force generator
faster
Prestin works by binding and shuttling intraceullar anions (Cl - chloride) ______ the extracellular surface
toward
When does this binding and shuttling of intracellular anions toward the extracellular surface take place?
following hyperpolarization
When does this binding and shuttling of intracellular anions toward the intracellular surface take place?
depolarization
Prestin also works by binding and shuttling intraceullar anions (Cl - chloride toward the _________ surface
intracellular
electrical signals (those Prestin relies on) are probably derived from OHC stimulation, with input from the __________ fibers that innervate the OHCs
efferent (OCB) fibers
what are the functional significances of OHCs? (3)
a) cochlear amplifier
b) equalization
c) tone-on-tone suppression
the cochlear amplifier can __________ sound levels
increase
cochlea amplifier increases sound levels up to 1000 fold at lowest sound levels and decreases with ____________ stimulus intensity
intensity
allows the perception of 2 sufficiently diff frequencies within a stimulus, indepdent of their intensity
equalization
equivalent to lateral inhibition seen in eye and other neural structures (allowing for even sharper tuning of BM)
tone on tone suppression
what is another term for tone on tone suppression
frequency masking
what is frequency masking
process inhibits neighboring or adjacent regions (frequencies) to highlight the most prominent
what exactly is the frequency masking
fine tunes/suppress/cancels adjacent vibrations of regions
- 2 similar tones may mask one another
all receptor cells, regardless of receptive field, work as _________ to convert some form of physical or chemical energy to a form that can be conveyed by a neuron to CNS
signal transducers
because of the speech with which ions start to flow into the sensory hair cell following deflection of stereocilia, it has been assumed that the mechanism responsible must rely on mechanical control of the ________
gating mechanism
tip links of the gating mechanism: what are they?
strands of extracellular glycoprotein
- Cadherin-23
- Protocadherin-15
the tip link extends from _____ of one stereocilia to the ________ of an adjacent
taller stereocilia
tip; side
tip link is most likely somehow inserted into a ___________
mechanically gated ion channel (MET)
what does the MET allow?
change in membrane potential
- K+ ions into cell
gating mechanism drawing
what other component of sensory mechanotransduction machinery have been identified? (3)
tetraspan membrane protein in hair cell stereocilia (TMHS)
transmembrane inner ear
(TMIE)
transmembrane channel-like proteins 1 and 2
(TMC1/2)
Deflection of the hair bundle toward the tallest stereocilia leads to an ______ in the probability of MET channel opening, while deflection in the opposite direction _______ channel open probability.
increase; decrease
what could impact MET channel opening?
- deflection of hair bundles
- changes in OHC height
- MET channel is nonselective for cations, but increased activity when external calcium is decreased (like endolymph)
signal transduction summary
1) Fluid forces elicit traveling waves along BM
2) Shearing force causes stereocilia deflection
3) Tip links become taut
4) MET channels open
5) Nonselective cation flow (K+ ions into hair cell)
6) hair cell depolarization
7) Voltage gated Ca+ channels open
8 Ca+ neurotransmitter vesicles move to BM & fuse releasing glutamate into synaptic cleft shared with SGN
9) Receptors on afferent nerve bint NT → SGN produce 1st AP
what other mechanisms could be at play with signal transduction?
- other ion channels/complexes
- additional channels that fine tune calcium-initiated vescile response + promote repolarization
- mechanisms of adaptation of the MET channel
- how OHC motility affects probability of MET channel opening
(all must be further researched)
