Unit 2 - Lecture 1 Flashcards
What are the 5 arteries that supply blood to the inner ear?
- Subclavian arteries (main artery that comes off the left ventricle)
- Vertebral arteries
- Basilar artery (vertebrobasilar system)
- Anterior inferior cerebellar artery
- Internal auditory A (goes into internal auditory meatus)
- Anterior vestibular artery
- Common cochlear artery- Main cochlear artery
- Posterior vestibular artery
The anterior vestibular artery goes into the ____
Common cochlear artery
The blood flow can be limited by the degenerative change of ____
Vertebrae
What happens to the blood through the vertebrae when you age?
Blood supply through this branch when you age is reduced and can call vertebral attacks
Subclavian artery comes directly from the ____
Heart
Basilar artery is formed from the ____ artery
Vertebrae
Which provides blood supply to the cochlea?
Main cochlear artery
What does the basilar artery branch into?
Anterior inferior cerebellar artery
What does the anterior inferior cerebellar artery branch into?
Internal auditory artery
What does the internal auditory artery branch into?
Anterior vestibular artery and common cochlear artery
What does the anterior vestibular artery and common cochlear artery branch into?
Posterior vestibular artery
The common cochlear artery becomes the ____
Spiral artery in modiolus
Common cochlear artery rotates around the ____
Modiolus
Where does the spiral artery in the modiolus supply blood too?
Supplies blood to the cochlear turns as far as the lateral wall (becomes thiner and thiner as it goes up becoming a capillary artery)
Explain the blood supply to the cochlear from the cochlear artery (spiral modiolar artery)
- Modiloar blood bed (supplies to ____)
- VSBM (vessels of basilar membrane) may supply ____
- Radial A. to lateral wall supplies ____
- Capillary network to collecting vein to ____ vein-back to larger vessels
- Modiloar blood bed (supplies to SGNs)
- VSBM (vessels of basilar membrane) may supply organ of corti
- Radial A. to lateral wall - stria vascularis and others
- Capillary network to collecting vein to spiral modiolus vein-back to larger vessels
No direct contact between ____ and ____ to ____
blood vessels, Organ of Corti, avoid noise from blood flow
What would happen if blood was actively pumping to the organ of corti? What happens when it isn’t working properly?
If blood was actively pumping to the OC, it would stimulate the hair cells (objective tinnitus happens when this isn’t working properly)
What are the 7 branches?
- To corner between spiral ligament and reissner’s membrane
- To scala vascularis
- To spiral Prominence
- To spiral ligament
- To spiral limbus
- To VSBM + spiral lamina
- To spiral ganglion
7 branches - Corner between spiral ligament and reissner’s membrane
Important for generation of perilymph, cochlear metabolism, and a lot of blood
7 branches - Stria vascularis
- Goes to the stria vascularis
- Important for cochlear metabolism, most energy from the blood supply is spent here (because of the battery theory), a lot of blood
- Majority of blood supply
7 branches - Spiral Prominence
- Between BM and lateral wall (projects to scala media)
- Contains fibrocytes (important roll in recycling potassium back into the SV)
7 branches - Spiral ligament
- Most lateral (supplies blood to spiral ligament)
- Located laterally to the SV
- Not super active in terms of metabolism so doesn’t require a lot of blood
7 branches - Spiral limbus
- Supplies the spiral limbus
- Bony, but fibrocytes on the surface
- Where perilymph is generated
7 branches - VSBM + spiral lamina
Goes underneath the BM, blood doesn’t go through BM, just below
7 branches - Spiral ganglion
Rosenthal canal to supply the SGN
- Capillary network is formed within Rosenthal canal, BM, and lateral wall of stria vascularis
- SV provides the most energy for the cochlea to be functional
Provides nutrition to SGNs, branches to the lateral wall (branches into 1, 2, 3, 4)
____ and ____ are very important for energy purposes
Stria vascularis, spiral ligament
Blood/energy supplies to the organ of Corti - nutrition from the VSMB
- Without this, the cells of organ of Corti will die.
- Nutrition is in the VSMB; No direct blood supply for sensory cells, they rely on diffusion.
- If VSMB is cut off from blood supply, OC will die as it maintains OC life.
Blood/energy supplies to the organ of Corti - What is energy for the HC’s dependent on?
Energy for the HC physiology is largely dependent on blood supply to stria vascularis and spiral ligament (lateral wall structures) — Without this, transduction and transmission of hair cells would not function.
How can you see the shape of the blood vessels in the cochlea?
- Inject liquid silicone into the blood vessels
- Goes through and we leave it there to harden
- Need to digest the structures to see the pathways that the silicone made (get rid of all soft tissue)
- Then you can see the shape of the blood vessels
Capillary Bed in lateral wall
RA: radiating arterioles
SMA: spiral modiolar arteriole
SMV: spiral modiolar vein
CV: collecting venules
Explain the 2 systems of capillary beds in the lateral wall.
We can see 2 types of blood vessels
1. Thin blood vessels inside the stria vascularis
2. Thicker blood vessels that go through the spiral ligament (for the whole scala media - go to the spiral ligament)
- Blood will be reduced through this branch (2) and go through the capillaries inside the scala vascularis when energy is needed (short cut - bypass) – when energy supply is not high blood will go through here
- The blood vessels in spiral ligament are thick and not needed for nutrition purposes (so why are they so big? Its an adjusting system - because blood vessels in lateral wall shares an origin with the SV so they can share if they need blood)
Who was homeostasis proposed by?
Walter Cannon
What is homeostasis?
- Stability and dynamic change of “internal environment” where cells live
- Big change in external environment, small variation in internal environment
Example of homeostasis
Big change in temperature outside, our body doesn’t change inside
What are special for inner ear to maintain homeostasis in cochlea?
Structures: three scalas, stria vascularis
Biochemistry: K transportation and distribution
Electrophysiology: Endocochlear potential
Homeostasis is invented from an ____ mindset
Engineering
What are the 3 types of cells in the stria vascularis?
- Marginal cells (M)
- Intermediate cells (I)
- Basal cells (B)
Explain tight junction along the stria vascularis
- Tight Junction along M cells and B cells
- Isolated space in St.V—Blood Labyrinth barrier (BLB)
- Active transportation of K from blood to endolymph
- Recycling by fibrocytes via gap junction
Where are the cells of the stria vascularis located?
- Basal cells are most lateral
- Inside is intermedial cells
- Facing the scala media is the marginal cells (most medially)
Inside of the stria vascularis is fully isolated from the ____.
Basal and marginal cells
Explain the blood labyrinth barrier
- Blood vessels on the lateral wall are separated from the liquid space of the cochlea (this is the blood labyrinth barrier)
- The material that goes through the capillary in the cochlea cannot really get into the cochlear fluid space, there is active transportation around potassium
What is gap junction?
Gap junction is another type of connection between cells (provides channel for certain material to pass)
What is the importance of fibrocytes?
For recirculation
Explain tight junction (what is the voltage difference)
Separation between Endolymph and Perilymph by tight junctionAcross the top of HC: 140 mV voltage difference
Does tight junction allow anything to pass?
No
Across the organ of corti, where is tight unction formed?
- At the level of the reticular laminal (top level of OC)
- Double layer around SV
The basilar membrane is largely permeable to ____
Perilymph
Tight junction forms an isolated space around ____
Stria vascularis
Why is there tight junction at the level of the reticular lamina?
Because there is a special environment for the HC
- Tops: stereocilia in endolymph
- Bottoms: in perilymph
Perilymph vs Endolymph
- Perilymph similar to extracellular fluid (low K, High Na), gradient along the turns and differences between SV and ST
- Endolymph similar to intracellular fluid (high K, low Na), hyperosmotic (total concentration of particles is relatively higher than perilymph), positive potential
- High K in Endolymph: for endocochlear potential formation, for transduction
Where is endolymph reabsorbed?
Endolymphatic sac is where endolymph is reabsorbed (important to maintain the amount of endolymph by balancing the generation and reabsorption)
What happens when endolymph doesn’t get absorbed?
When it doesn’t get absorbed, will get endolymphatic hydrops (associated with Meniere’s disease)
What is the voltage of endolymph?
+80mV
What is the voltage of perilymph?
-60mV
Is the concentration of perilymph in the scala vestibuli and scala tympani equal?
No, but the concentration between the two organs must be small
Perilymph, blood, and CSF are high in ____
Sodium
Endolymph is high in ____
Potassium
Barrier between blood and perilymph
Barrier between blood and perilymph is similar to blood-brain barrier seen in blood vessels
Things can get into the brain easier than the cochlear (exception can be drugs)
Evidence for the barrier
- Tracer kinetics (take time for tracer to get into periplymph from blood)
- Ion differences between the two compartments
- Specificity and competitive inhibition: existence of special transportation system
What does barrier specificity mean?
- Specificity means that the barrier selectively allow certain materials to pass, often related to special transportation system (i.e. by ion channels and transporter).
- Since those channels and transporters may be able to transport more than one materials, there is a competition between the materials: the transportation bias to the one with higher concentration and higher binding ability to the transporter.
Explain tracer kinetics?
- Can inject tracer directly into blood circulation (gets into blood then slowly into perilymph) – perilymph takes the tracer with a time delay showing that there must be a barrier
- Ion difference means that it doesn’t move freely between blood and perilymph (so there is a barrier)
What is perilymph filtered from?
Perilymph is filtered from blood, but not directly because there is a barrier
How is perilymph generated?
- Electrolytes movement followed by water (also true for endolymph)
- Generation of perilymph, electrolytes is the first movement
- Perilymph is generated by the movement of electrolytes
Is there bulk flow in the generation of perilymph?
- No bulk flow, generated locally and slowly, filtered from serum (blood)
- Movement is very slow
What are the generation sites of perilymph?
supra-ligament area, and supra-limbus area
What are the reabsorption sites of perilymph?
below BM at the medial and lateral corner
What are the cells of perilymph generation?
Fibrocytes (stromal cells): Local control of homeostasis, need more research in circulation
What are the active points for ion transportation?
- suprastria region
- supralibral zone
Generation of endolymph relies on active process for____ because equilibrium potential for K is ____
high [K], negative
What is the equilibrium potentials?
How much is the voltage difference to balance the driving force produced by the concentration difference.
Explain the concentration difference of K between endolymph and perilymph
The concentration diff of K between endolymph and perilymph drives K out from endolymph, voltage must be -89 mV in endolymph to stop this movement by the concentration difference. However, the voltage in endolymph is +80 mV, therefore, there must a driving force > 169 mV to push the K into endolymph from perilymph.
What are the two driving forces of K?
- Goes from high voltage side to low voltage side (direction of positive ion movement)
- Second driving force is concentration difference (moves from high to low concentration)
- The two driving forces may or may not work in the same direction
What is the voltage difference required to stop the diffusion of this ion?
Based on the concentration difference between endolymph and perilymph, we require the endolymph space to be -89 mV in order for the voltage difference to stop the diffusion by concentration difference
Larger difference between this value and reality is a larger driving force (reality is +80 mV –89 mV to stop diffusion)
Explain equilibrium potentials
The voltage difference to counter-balance the driving force by the concentration difference
Example for K
- [K] diff between endolymph and perilymph drives K out from endolymph
- The equilibrium potential for K in endolymph is -89 mV, which means that the voltage there must be so negative in order to balance the K movement by the [K] diff.
- The reality is +80 mV in endolymph: far away from balance, resulting, a strong tendency for K to move from SM to ST
-89 mV is what it would take to get it to not happen (but we have +80 mV so that doesn’t actually happen)
Source of Endolymph
- what’s exchanged?
Directly from perilymph, not blood
- K and Cl exchange
- Different effect of K-free perfusion in perilymph spaces and blood vessels
Stria vascularis and endolymph generation
- Fluid (EL) moves slowly to endolymphatic sac, where re-absorption occurs
- Potassium is moved from stria vascularis to endolymph to produce DC potential in SM (endocochlear potential), a process requiring energy –> energy supply comes from the material in the blood from stria vascularis
- function of marginal cells is identified by exp.
Transportation and generation of endolymph occurs at the ____
Stria vascularis
What is davis battery theory also called?
Also called variable resistance theory
Explain the davis battery theory
Two batteries
- Big one at StV for EP (provides high concentration of K and maintains 80 mV potential - important for endocochlear potential)
- Small one at HC membrane for intracellular potential (Maintains the negative potential of the HC)
Two batteries are in serial connection with the variable resistance—MET channels
What is standing current?
Standing current (without sound)
- Goes across the cochlea
- Stria vascularis – scala media – organ of corti – scala tympani – and back to stria vascularis
- The current that goes across reissner’s membrane is much smaller
Current will be increased or decreased depending on the ____
Sound
What are the advantages of K as carrier for transduction current?
- Downward movement from endolymph to HC to perilymph (no immediate requirement for energy, reduce noise) –> biggest advantage
- Little disturbance of cytosolic homeostasis (what happens inside the hair cells in terms of ion concentration)
- K+ channels on basal-lateral wall of OHCs provide transduction current and maintain resting potential
____ is one of the most sensitive organ in the whole body to damaging factors
OC
____ channel is not ion selective, but the ____ channel is selective
MET, K+
Bioengineering of cochlea
- The major energy generation site ____ is away from the transduction site ____
- The negative intracellular potential is mainly generated by ____, the need for the ion pump (the small battery) across HC membrane is ____.
- There is no blood supplies directly to the ____ (the nutrition needs from ____ across BM)
- MET is a ____ procedure
- All those limit ____ noise.
- However, those also put critical cochlear cells in the risk of energy crisis when the demand is high—one of the reasons for HCs to be sensitive to damaging factors.
- The major energy generation site (Stria vascularis) is away from the transduction site (MET channel)
- The negative intracellular potential is mainly generated by K diffusion, the need for the ion pump (the small battery) across HC membrane is small.
- There is no blood supplies directly to the organ of Corti (the nutrition needs from diffusion across BM)
- MET is a passive procedure
- All those limit biological noise.
- However, those also put critical cochlear cells in the risk of energy crisis when the demand is high—one of the reasons for HCs to be sensitive to damaging factors.
Endocochlear potential generation mechanism (what is the voltage recorded when the electrode penetrates the lateral wall of cochlea)
- Voltage recorded when electrode penetrates the lateral wall of cochlea
- The DC potential in marginal cell is 5-10 mV higher than that in SM (90 mV compared to 80 mV)
Explain the microelectrode used to record potential
- Microelectrode is used to record potential (small shell on the bony shell is removed so microelectrode can be inserted)
- Potential is recorded relatively to the potential inside the scala tympani
- When the pentration gets into the marginal cells there is a big jump of potential
- When the probe was just going in, they were measuring 90 mV, but when it went all the way in it was 80 mV
One-pump two-cell model
- This was proposed to understand the generation of endocochlear potential
- For EP to be generated 2 cells need to work together (1. MC and 2. IC + BC)
- Pump
- Moving across voltage difference (need to move uphill - requires energy supply from blood)
- Moves K and Na
- Pink channel (MC)
- Special K channel located at MC surface facing EL (SM)
- Allows diffusion of K from MC to EL
- KCNE1/KCNQ1 = related to genetic hearing loss
- Purple channel (IC + BC)
- Faces the space
- Generation of EL
- K diffusion channel on intermediate cells (all downward)
- KCNJ10 = can also cause hearing loss
One-pump two-cell model - where is the positive pump located?
The positive pump is located in the intrastrial surface of marginal cells
What does the positive pump transport?
Potassium into marginal cells
Channel allowing diffusion of potassium is ____
KCNE1
EP generation
- EP generated across KCNJ10 K channels
- Marginal cells produce extremely low [K] in intrastria space, where V= 90 mV
- Facilitating K diffusion through KCNJ10 K channels to generate EP
Evidence for KCNJ10 K channel
- EP is found across basal cell barrier
- Intermediate cells have gap-junction with basal cells as K pathway to StV
- K equilibrium voltage across intermediate cells is 120 mV, favoring K out to intrastria space
- Data from channel manipulation: blockers, gene knockout etc: dysfunction of KCNJ10 K causes hearing loss.
Role of Marginal cells
- Energy consuming pump at MC provides energy for EP generation
- K is pumped into MCs to maintain low K in intrastrial space
- Co-transporter
- No Na conductance at marginal cells, but Cl conductance
- K diffusion from MC to endolymph through KCNQ1/KCNE1 channel
K Recycling: perilymph to stria vascularis
- where does recycling go through
- recycling via…
- what’s an easy pathway
- ____ at ____ are involved
- what is the bridge between endolymph and intrastria space?
- what do fibrocytes have a gap junction with?
- From endolymph to SV and ST and then stria vascularis, not to blood
- Recycling via supporting cells in OC and around spiral ligament,
- gap-junction: easy pathway
- Fibrocytes at spiral prominence involved
- Claudius cells are bridge between endolymph and intrastria space, contacting fibrocytes
- Fibrocytes have gap junction with basal cells of stria vascularis
Recycling of potassium largely occurs through ____
gap-junction
Gap Junction—intercellular connection, directly connect cytoplasm (how is it made, where is it mostly located)
- Hetero-hexamers of connexin proteins
- Hetero: different, hexamer: a structure with 6 units.
- Gap junction is mostly located between HC and supporting cells (and supporting cells and fibrocytes)
- Made with connexin proteins
Gap Junction Functions (4)
- Electrical and metabolic coupling
- Tumor suppressor
- Adhesive function
- Carboxyl-terminal in signaling cytoplasmic pathway
Gap junction exists between ____ and ____
hair cells, supporting cells
There are more than ____ types of gap junction proteins and genes in the whole body
22
What are the dominant gap junction proteins and genes in the cochlea
CX26 and CX30 dominant in cochleae
____ are really important and can cause hearing loss
Proteins
Mutation of GJB2 and 6
- type of HL
- prevalence
- degree for each
- carrier rate for each
- heterozygote
- Type of hearing loss: autosomal non-syndromic, recessive
- Prevalence: ~50% (in total of autosomal non-syndromic hearing loss), mainly GJB2
- Degree of hearing loss:
GJB2: profound at birth
GJB6: mild to moderate, progressive - Carrier rate: 1-4% for GJB2 mutation, 1% for GJB6 mutation
- Heterozygote at one (either GJB6 or 2) does not cause HL, but double heterozygote mutation does
Mutation of ____ gene wont cause hearing loss, but mutation simultaneously of ____ genes will cause hearing loss
one, two
Many HL-associated mutation of Cx26 does not disrupt ____ recycling
K
The gap junctions still exist and work after ____ gene knockout.
One
If ____ is mutated later in development, HCs are okay.
Cx26
Normal Cx function is required in critical period for ____
normal development
Late-onset, progressive HL with Cx mutation:
Damage in active amplification, not the recycling, causes hearing loss.
____ mutation causes developmental abnormality in OC, especially HCs.
Cx
