Kretzer Inner Ear Lectures

Front 1

What are the six sites where the membranous labyrinth is differentiated into hair cells and give the function of each.

Back 1

1. on the cristae (7000 hair cells) across ampulla at three sites in each semicircular canal - detects angular accelerations/decelerations
2. on macula of utricle (1000 hair cells) - detects horizontal accelerations/decelerations (standing up in a moving bus)
3. on macula of saccule (1000 hair cells) - detects vertical accel/decel (going up and down in an elevator)
4. in the organ of Corti (3,000 inner hair cells; 3 rows of outer hair cells 3,000/row; 12,000 hair cells total) - hearing (inner row for hearing)

Front 2

Describe the unique shape of the macula of utricle vs. macula of saccule

Back 2

macula of utricle - kidney shaped
macula of saccule - hook shaped

Front 3

Name the accessory structure of the cristae across each ampulla in each SC canal

Back 3

cupula (gelatinous mucopolysaccharide) - totally closes off the canal

Front 4

Name the major neurotransmitter released at the synapses with hair cell activation.

Back 4

glutamate

Front 5

Define hair bundle

Back 5

complex found at the apical surface of hair cells facing endolymph; composed of one kinocilium and 4-5 rows of stereocilia that act as one viscoelastic unit

Front 6

What's the concept behind endolymph vectors and the hair cells of the crista in each ampulla?

Back 6

Concept is that with low energy endolymph vectors, only the hair cells at the tip of the crista are impacted. In contrast, with high energy endolymph vectors, the total cupula is deformed, and all the hair cells “on the mountain” are impacted. Cells at the bottom of the cristae (dark cells because of their high mitochondrial content) secrete endolymph.

Front 7

What's the concept behind endolymph vectors and the hair cells found in both maculas of utricle and saccule?

Back 7

With endolymph vectors, these otoconia deform the proteinaceous “membrane” that impacts on the hair cells. A high energy endolymph vector can move the large and small otoconia. A low energy endolymph vector can only move the smallest otoconia.

Front 8

Define: otoconia

Back 8

various sized calcium carbonate rocks (3-19 microns in diameter) that deform proteinaceous membrane that impacts on the hair cells (macula of utricle/saccule)

Front 9

What happens with normal aging to the otoconia?

Back 9

With normal aging, the otoconia become uniformly homogenous (uniformly 6 microns at age 60 years) with less balance sensitivity. Often some of the otoconia become loose from the otolithic membrane of the macula of the utricle and become embedded in the cupula of the latera (horizontal) semicircular canals producing a common “positional vertigo” in the elderly when they roll to get out or into bed. Their gait gets wider and wider b/c balance not as precise.

Front 10

What happens with heavy endolymph movement against the cupula and the hair bundle deflects directly toward the kinocilium?

Back 10

more and more of the 7000 hair cells in the "mountain" are recruited and this causes max depolarization

Front 11

Define hair cells and give their origin.

Back 11

highly differentiated epithelial cells which have become mechanoreceptors in the inner ear; ectodermal origin (cytokeratin pos)

Front 12

Characterize hair cells in terms of their ability to enter cell cycle.

Back 12

post-mitotic, nonregenerating cells

Front 13

Hair cells are ____ order neurons with/without dendrites or axons.

Back 13

1st; WITHOUT dendrites or axons

Front 14

How are the hair cells situated within tissue?

Back 14

They reside as a single epithelial layer separated by supporting cells and the cells of the membranous labyrinth that enclose the space housing endolymph.

Front 15

Describe junctional complexes associated with hair cells. Give functions of each type.

Back 15

They have tight junctions at their apical lateral surface which seals the endolymph at their apical surfaces from the perilymph which baths their basolateral and basal plasma membranes.

Below the tight junctions are adherent junctions from which actin filaments form the highly modified terminal web called the cuticular plate.

No desmosomes! (bc no friction)
No gap junctions!

Front 16

Define duplicity.

Back 16

the fact that there are 2 types of hair cells

Front 17

Characterize the 9+2 axoneme of kinocilium. Why do patients with Kartagener's syndrome have no problems with hearing/balance?

Back 17

non-motile (no dynein arms, no nexin links, no radial spokes/spokeheads, etc.)

bc it's non-motile, patients with immotile cilia syndromes (Kartagener's) have no dysfunction within the inner ear hair cells -- no hearing/balance disturbances

Front 18

How does kinocilium work?

Back 18

it receives the tension from endolymph induced defections of the cupula (crista in the ampullas of SC canals) and of the otolithic membrane (maculas of utricle/saccule)

Front 19

What is the important relationship of the kinocilium to the hair bundle? What does the height of the hair bundle have to do with its component stereocilia?

Back 19

kinocilium establishes the axis of bilateral symmetry of the hair bundle and the height of the hair bundle. The height of a hair bundle determines the diameter of its component stereocilia with the core of bundled actin that inserts into the cuticular plate. This is one important component of mechanical tuning of hair cells.

Front 20

How often does the development of hair bundle take place in the human lifetime?

Back 20

ONCE!

Front 21

Describe the way that glutamate is released from the hair cells.

Back 21

At the basal surface of hair cells (except outer hair cells of the organ of Corti), there are synaptic vesicles which release glutamate triggered by voltage gated, calcium channels which cause synaptic vesicle migration, exocytosis, and release of glutamate.

Front 22

Why is the term "stereocilia" totally incorrect?

Back 22

they are actually highly modified microvilli-- but don't have anything to do with axonemes

(There is a constant renewal of their bundled actin filament core structure throughout life.)

Front 23

Characterize the way stereocilia are

Back 23

arranged in 4-5 rows, with tallest stereocilia next to the kinocilium. all hair cell bundles have a step ladder configuration (very cool!)

Front 24

Characterize the stereocilia within a hair bundle with the kinocilium that is very tall (100 microns).

What if the kinocilium in the hair bundle is short?

What does this have to do with anything?

Back 24

K tall (100 micron)- they will all be very thin (small diameter - 0.2 micron)

K short (3 micron) - they will all be fat (large diameter -1 micron)

short, fat guys are hard to bend; tall, thin stereocilium are easier to bend

Front 25

Give the ranges of height for kinocilium.

Give the range of diameter for stereocilium.

Back 25

K = 3-100 microns
S = 0.2-1 microns

Front 26

• Why must all hair bundles be some form of a truncated structure?

Back 26

So they can bend uniformly with pressure from the endolymph;
To let the springs do their things so you can push in one direction or another

Front 27

What is the significance of hair bundles that are short and fat as compared with those that are tall and skinny?

Back 27

The short (3u), fat (1u) stereocilia have many microfilaments which insert into the cuticular plate at the basal constriction point and give such a bundle great rigidity.

• In contrast, the tall (100u), skinny (.2u) stereocilia have very few microfilaments which insert into the cuticular plate at the basal constriction point and give such a bundle great flaccidity.

Front 28

How do the stereocilia appear?

Back 28

All stereocilia in any given hair cell exists in rows of identical heights. The row of the shortest stereocilia is furthest from the kinocilium. Each progressive row of stereocilia is taller than the row in front of it.

Front 29

About how many stereocilia are on each hair cell?

Back 29

~100

Front 30

How does the gating spring and transduction channel thing work with stereocilia?

Back 30

There is one transduction channel at the tip of the stereocilia. From that one tip is a gating spring that attaches to the next row of stereocilia. So the stereocilia bends with each other, this puts tension on gating spring and makes the transduction channel stay open more of the time so more potassium can rush in. hair cell depolarizes. More glutamate is released. If I were to push stereocilia away from the kinocilium, the channel remains closed more of the time, less K comes in, hyperpolarizing the hair cell, less glutamate.

Front 31

How does the hair bundle induce maximal depolarization of hair cells?

Back 31

When the hair bundle is deflected directly toward the kinocilium on the axis of bilateral symmetry, maximal depolarization occurs.

Front 32

What does off-axis depolarization do and where does this occur?

Back 32

Hair bundle deflection off axis creates less depolarization, until hair bundle movements at right angles to the axis of bilateral symmetry established by the kinocilium creates NO
depolarization whatsoever.

A graded off-axis depolarization occurs only in the macula of the utricle and the macule of the saccule.

Front 33

Where on-axis maximal depolarization found?

Back 33

On axis, maximal depolarization is found in the semicircular canals, in the three rows of outer hair cells in the organ of Corti, and in the one row of inner hair cells in the organ of Corti.

Front 34

How does the hair bundle induce maximal hyperpolarization of hair cells?

Back 34

When the hair bundle is deflected on-axis away from the kinocilium, the nonspecific transduction channels are closed more of the time because the tension in the gating spring is lessened.

With hyperpolarization, less glutamate is released, and the number of action potentials per unit time drops BELOW resting tonic levels.

Front 35

Describe the cristae in the ampulla of semicircular canals in terms of - Type I/type II distribution, nature of the hair bundle, presence of a kinocilium in the adult, only on-axis depolarization/hyperpolarization, potential for off-axis depolarization/hyperpolarization, somatic electromotility, and accessory structures.

Back 35

- mixed presence of type I/type II hair cells
- all hair bundle (kinocilium) uniformly point toward utricle; mixture of short/fat and tall/skinny hair bundles at every point
- ONLY on-axis depolarization and on-axis hyperpolarization depending upon now the endolymph deforms the cupula.
- Cupula - accessory structure found here

Front 36

Describe the macula of the utricle in terms of - Type I/type II distribution, nature of the hair bundle, presence of a kinocilium in the adult, only on-axis depolarization/hyperpolarization, potential for off-axis depolarization/hyperpolarization, somatic electromotility, and accessory structures.

Back 36

- presence of type I and II
- Type I hair cells with tiniest otoconia at the striola line
- mixture of short/fat and tall/skinny hair bundles at every point
- kinocilium of the hair bundles CONVERGE at the striola line (bend towards the striola line to depolarize hair cell)
- CAN undergo off-axis depolarization/hyperpolarization (which gives tremendous sensitivity of these 1000 hair cells to horizontal linear accelerations)
- accessory structures: otoconia and proteinaceous membrane

Front 37

Describe the macula of saccula - Type I/type II distribution, nature of the hair bundle, presence of a kinocilium in the adult, only on-axis depolarization/hyperpolarization, potential for off-axis depolarization/hyperpolarization, somatic electromotility, and accessory structures.

Back 37

- presence of both type I and II
- type I cells (flask-shaped) with tiniest otoconia enriched at striola line
- hair bundles DIVERGE relative to striola line of the hooked shaped structured (bend away from each other for depolarization of hair cell)
- CAN undergo off-axis depolarization/hyperpolarization
- accessory structures: otoconia and proteinaceous membrane

Front 38

Increased tension on the gating spring INCREASES/DECREASES the probability that the channel will be open (favors increased depolarization of the hair cell). In contrast, decreased tension on the gating spring INCREASES/DECREASES the probability of pore closure and thus of increased hyperpolarization.

Back 38

decreases; increases

Front 39

Characterize the inner hair cells of organ of Corti in terms of: Type I/type II distribution, nature of the hair bundle, presence of a kinocilium in the adult, only on-axis depolarization/hyperpolarization, potential for off-axis depolarization/hyperpolarization, somatic electromotility, and accessory structures.

Back 39

- one row of 3000 inner hair cells purely flask shaped (type I) that sit on tympanic lip of osseous spiral lamina
- do NOT have short/fat to tall/skinny morphologic gradient from base to apex of cochlea
- uniform step ladder wall function to receive endolymph jet
- stereocilia bundle with tallest stereocilia facing stria vascularis -- NO KINOCILIUM IN ADULT (Their tallest stereocilia does NOT insert into the tectorial membrane.)
- depolarize on-axis ONLY in response to endolymph jet (to secrete glutamate)

Front 40

Characterize the outer hair cells of organ of Corti in terms of: Type I/type II distribution, nature of the hair bundle, presence of a kinocilium in the adult, only on-axis depolarization/hyperpolarization, potential for off-axis depolarization/hyperpolarization, somatic electromotility, and accessory structures.

Back 40

- 3 rows of 3,000 hair cells each
- pure segregated cylindrical shaped (type II), sit on basilar membrane
- at maturity have only a stereocilia bundle with the tallest stereocilia facing the stria vascularis (no kinocilium)
- gradation from short/fat stereocilia bundles at base which change to tall/skinny stereocilia bundles at apex
- ON-AXIS DEPOLARIZATION ONLY with relative shear by tectorial membrane with resultant somatic electromotility shortening

Front 41

What is so exciting about the recent research breakthrough of the viral transvection of the gene that triggers hair cell differentiation from supporting cells of the membranous labyrinth of the inner ear? What are its shortcomings?

Back 41

in guinea pigs, it is now possible to induce new hair cell development from the adjacent supporting cells if they are virus transvected with the single gene that causes the developmental sequence of hair cells. It is not known if these new hair cells are properly mechanically tuned, correctly display an organized axis of bilateral symmetry, or if second order afferent neurons synapse on the basal surface.

Front 42

Tell me about the kinocilium in the hair cells of the organ of Corti

Back 42

they involute at maturity, leaving only the basal body remnant that was its nucleation center (MTOC).

Front 43

Describe the stereocilia configuration in the organ of corti - 1) outer hair cells, 2) inner hair cells

Back 43

In the organ of Corti, only the tallest stereocilia of the outer hair cells insert into the tectorial membrane. No component of the hair bundle of the single row of inner hair cells on the bony tip of the tympanic projection of the osseous spiral lamina inserts into the tectorial membrane and is the only hair cell in the human body that DIRECTLY responds to endolymph movement.

Front 44

What is the location of the only hair cells that directly respond to endolymph movement?

Back 44

inner hair cells in the organ of Corti

Front 45

What's the difference between the way inner hair cells and outer hair cells of the organ of Corti are depolarized?

Back 45

inner hair cells - endolymph jet DIRECTLY causes depolarization along the stereocilia bundle

outer hair cells - tallest stereocilia insert into the tectorial membrane for on axis depolarization

Front 46

Scala vestibuli is separated from scala media by ________ membrane and filled with PERILYMPH/ENDOLYMPH. It communicates with scala tympani at apex of cochlea via the _________.

Back 46

Reissner's (single layer of tight-jxn linked epithelial cells); perilymph; helicotrema

Front 47

Scala tympani terminates at the ______ window and is separated from scala media by the ________ membrane.
Filled ENDOLYMPH; PERILYMPH.

Back 47

round; Basilar; perilymph

Front 48

Scala media is a triangular structure delineated by what 3 things?

Back 48

Reissner's membrane, stria vascularis, basilar membrane

Front 49

Scala media is filled with ENDOLYMPH/PERILYMPH secreted by _____________.

Back 49

endolymph; stria vascularis

Front 50

Describe the basilar membrane

Back 50

the basilar membrane is tight and rigid at the base of the cochlea (mechanically tuned to 20,000 Hz) and progressively becomes more floppy and flaccid at the apex of the cochlea (mechanically tuned to 20 Hz)

Front 51

Characterize the epithelium of the stria vascularis

Back 51

pseudostratified columnar epithelium uniquely invaded by melanocytes (essential for endolymph secretion and explains the hearing loss in albinos or people with neural crest suppression of melanocyte migration) and by capillaries

Front 52

Describe the neurons associated with the inner hair cells of the organ of Corti

Back 52

all bipolar afferents (30,000 neurons) contact the base of the inner hair cells

Front 53

5000 Hz= CONSONANT/VOWEL?
800 HZ=CONSONANT/VOWEL?

Back 53

CONSONANT
VOWEL

Front 54

What happens when you hear 5000 Hz?

Back 54

- it vibrates on tympanic membrane
- lever system of middle ear ossicles transfers the vibration to perilymph in the vestibule ==> travel up scala vestibuli and at one unique spot does the rigidity of the basilar membrane match the 5000 Hz vibration, and then the depression of Reissner’s membrane is yolked to a depression of the basilar membrane which bows down into the scala tympani. This causes the round window to bulge out into the middle ear. When this traveling wave maximally deforms this unique spot from the base to the apex of the cochlea, the inner hair cells on the tympanic lip of the osseous spiral lamina are impacted, release more neurotransmitter which causes an increased rate of action potentials in the second order afferent neurons synapsing on this inner hair cell.

Front 55

How is a depression in Reissner’s membrane yoked to a depression of the basilar membrane which is yoked to a bulging of the round window out into the air filled middle ear?

Back 55

It is only when you yolk a depression in Reissner’s membrane to a depression in the basilar membrane with a round window deflection into the middle ear that you can hear.

Front 56

Bell's Palsy patients will report what 3 things?

Back 56

1. the world is really loud - Hyperacusis (ASR)
2. my voice is weird - prevocalization reflex
3. i have trouble understanding speech - vowels aren't toned down bc vowels aren't being masked down

Front 57

What's the first thing that recovers after CN 7 recovers?

Back 57

acoustic stapedial reflex (stapedius is working again)

Front 58

Really define presbycusis.

Back 58

normal age related deterioration of hearing acuity due to elderly losing hearing sensitivity to high frequencies and consonants-- basal hair cells which are tuned to higher frequencies are used the most.

Front 59

tell me about the enzymes that repair hair cells.

Back 59

there are 5 enzymes that maintain/repair hair cells throughout entire life

Front 60

define calcium induced toxicity

Back 60

when calcium channels are always on with loud constant sounds --> eventually kills off hair cells

Front 61

What is meant by the statement that “vowels pass over the consonants in the traveling wave” along the tonotopic map of the organ of Corti?

Back 61

hearing is a traveling wave – where vowel travels over the consonants – vowels heard more toward the apex tuned to lower Hz’s. so vowels travel over consonants.

Front 62

What are the causes of hair cell death?

Back 62

- calcium induced toxicity (constant loud sounds)
- there's more...

Front 63

What 3 things happen with normal aging to your ears?

Back 63

- calcification of outer1/3 cartilage of external acoustic meatus
- normal otosclerosis -calcification of annulus
- presbycusis - massive decrease in acuity of consonants

Front 64

Outer Hair cells sit on _________
Inner hair cells sit on ________

Back 64

basilar membrane
BONE (of the OSL)

Front 65

Define somatic electromotility

Back 65

when the outer hair cells of the organ of Corti SHRINK as they become depolarized bc they are sheared relative to the tectoral membrane

Front 66

Describe how the whole process of outer HCs becoming depolarized and then leading to depolarization of inner HCs works.

Back 66

When basilar membrane drops, the 3 rows of outer HC become depolarized bc they are sheared relative to the tectoral membrane - on axis. They SHRINK -- this is called somatic electromotility. As the shrink, they throw endolymph vector under tectorl membrane that comes back and hits inner hair cells to become depolarized. Endolymph jet created by shrinkage of outer hair cells-- depolarizes on axis the inner hair cell and cause glutamate to be relaesd into the second afferent which is auditory branch of CN 8. We hear with 3,000 hair cells sitting on bone (timpanic lip OSL). It is the only hair cell that responds directly endolymph!! Here the inner hair cell becomes depolariezd by endolymph jet.

you are only supposed to know that the inner hair cells sit on bone (tympanic lip of the osseoeus spiral lamina), that they do not touch the tectorial membrane and that they have nothing to do with the basilar membrane. In contrast, the three rows of outer hair cells in the organ of Corti experience a depolarizing shear when the basilar membrane drops and this causes a relative shear of their hair bundle against the tectorial membrane which causes a somatic electromotility that causes these three rows of outer hair cells to throw an endolymph jet or vector under the tectorial membrane, around the inner tunnel, which causes a depolarization of the inner hair cells that let you hear that frequency (from kretzer)