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CMSD5280 Audition ll > Cochlear Physiology II: Blood Circulation and Homeostasis > Flashcards

Cochlear Physiology II: Blood Circulation and Homeostasis Flashcards

Anatomy Homeostasis Metabolism of both fluids EP generation and maintenance Recycling-gap junction Genetic hearing loss with Cx mutation

1
Q

Which arteries supply blood to the ear? (5)

A

Subclavian arteries
Vertebral arteries
Basilar artery (vertebrobasilar system)
Anterior inferior cerebellar artery
Internal auditory A (goes in interal auditory meatus

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2
Q

Where does the Internal auditory artery goes to? (5)

A
  • It goes in the interal auditory meatus
  • The Anterior vestibular artery
  • Common cochlear artery
  • Main cochlear artery
  • Posterior vestibular artery
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3
Q
A
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4
Q

Which branch of the Basilar artery/internal auditory artery supplies the cochlea?

A

Main Cochlear Artery

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5
Q

Where does the cochlear artery passes by in the cochlea?

A

Spiral modiolar A

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6
Q

Describe the Spiral modiolar artery (3):

A
  • Modiolar blood bed (supplies to SGNs)
  • From the Radial A. to the lateral wall—stria vascularis and others
  • It goes from the Capillary network to Collecting Vein to SMV back to larger vessels
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7
Q

Explain the contact between blood vessels and Organ of Corti

A

No direct contact between blood vessels and Organ of Corti (avoiding noise from blood flow)

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8
Q

Describe the 7 branches and their target

A

To corner between spiral ligament and RM (1):
To SV (2):
To spiral Prominence (3):
To Spiral ligament (4):
Spiral limbus (5):
VSBM +spiral lamina (6):
Spiral ganglion (7):

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9
Q

Describe the importance of the Capillary Bed in the lateral wall and its 4 parts :

A

The capillary bed in the stria vascularis is essential for solute homeostasis and preventing the influx of toxic substances into the inner ear

RA: radiating arterioles
SMA: spiral modiolar arteriole
SMV: spiral modiolar vein
CV: collecting venules

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10
Q

How do we study the blood flow in the cochlea?

A

We use silicone to mold and let dry

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11
Q

Explain the Capillary network the in lateral wall: (3)

A
  • We can see two types of blood vessels
  • Thick vessels in the spiral ligament provide a short circuit, to adjust the blood flow via stria vascularis.
  • They serve as a shortcut when the energy is low in the cochlea
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12
Q

Explain the concept of Homeostasis :

A

Walter Cannon
Stability and dynamic of internal environment - where cells live

Big Change in external environment small variation internal environment

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13
Q

What are the special needs of the IE to maintain homeostasis?

A

Structures: three scalas, stria vascularis
Biochemistry: k transportation and distribution
Electrophysiology: Maintain Endocohlear potential

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14
Q

Which are the 3 types of cells in the Stria Vascularis?

A

Basal Cells
Intermediate Cells
Marginal Cells

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15
Q

Explain the tight junctions in the Stria Vascularis: (3)

A
  • There is a tight junction along M cells and B cells, isolated space in St.V a Blood Labyrinth barrier (BLB) which material can’t get easily into the cochlea.
  • The tight junction is important for the active transportation of k from the blood to endolymph.
  • Recycling by fibrocytes via gap junction
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16
Q

Explain the tight junctions in the OC between the fluids:

A
  • The tight junctions allow the separation between endolymph and perilymph.
  • Helps to maintain the voltage difference across the top of HC of 140 mV between the two regions
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17
Q

What is special about the tight junction of the OC?

A

Tight junction does not allow anything to pass.
Across the OC, tight junction is formed at the level of reticular lamina NOT formed at the BM because it is impermeable

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18
Q

Describe Perilymph:

A

Perilymph similar to extracellular fluid (low K, High Na), gradient along the turns and differences between SV and ST
Connected to the CSF through Cochlear Acqueduct

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19
Q

Describe Endolymph:

A

Endolymph similar to intracellular fluid (high K, low Na), hyperosmotic, positive potential

Produced at the endolymphatic sac with the vestibule

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20
Q

Why is the High K in Endolymph important? (2)

A

For EP formation
For transduction

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21
Q

What is the role of the endolymphatic sac and what happens if there is damage to it?

A

Recycling of and Transportation of K
Cochlear Drops associated with Meiner’s desease

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22
Q

Explain the Similarities between the blood and perilymph barrier and the BBB:

A

The barrier is similar to the BBB seen in blood vessels: There are Pericytes among endothelial cells to form the barriers

Limitation of the blood barriers in the cochlea: Most of the material can get into the brain as compared to the cochlea

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23
Q

What are the roles of pericytes?

A

Cells are present along the walls of capillaries.
They are essential for blood vessel formation, maintenance of the BBB, regulation of immune cell entry to the CNS, and control of brain blood flow.

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24
Q

What is the meaning of the specificity of the barrier between blood and perilymph?

A

Specificity = The barrier selectively allows 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 material, there is competition between the materials: the transportation bias to the one with higher concentration and higher binding ability to the transporter.

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25
Q

Explain the EVIDENCE of the presence of a barrier between the blood and the perilymph: (3)

A
  1. Tracer kinetics: the tracer takes time to get into perilymph from the blood
  2. Ion differences between the two compartments
  3. Specificity and competitive inhibition: the existence of a special transportation system
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26
Q

How does the Perilymph gets generated?

A

Perilymph is generated locally and slowly and filtered from serum. The connection to CSF makes it easier to maintain the perilymph quantity.

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27
Q

What are the generation sites of perilymph?

A

supra-ligament area, and supra-limbus area

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28
Q

What are the reabsorption sites for perilymph?

A

below BM at the medial and lateral corner

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29
Q

What are electrolytes?

A

Electrolytes are chemicals that conduct electricity when dissolved in water. They regulate nerve and muscle function, hydrate the body, balance blood acidity etc.

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30
Q

What do Fybrocytis do?

A

Serve as local control of homeostasis, maintenance of biochemical status (the three regions in grey)

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31
Q

Explain the formation and homeostasis of endolymph:

A

Local control: very small flow rate («perilymph)

The generation of endolymph depends on Active process for high [K] because equilibrium potential between cochlea endolymph and perilymph for K is negative!

32
Q

What is Equilibrium potentials? Give an example for Potassium:

A
  • Asks how much is the voltage difference to balance the driving force produced by the concentration difference.

Example for K
[K] diff between endolymph and perilymph drives K out from endolymph
The K movement by the [K] diff is balanced voltage, which should be low in endolymph
How much? – 89 mV in endolymph
The reality is +80 mV in endolymph: far away from balance
Therefore, a strong tendency for K to move from SM to ST

33
Q

What are the movement forces that cause potassium movement? (2)

A

Diffusional force and Voltage difference

34
Q

Explain Diffusional Force:

A

Potassium moves from high to low concentration

35
Q

Explain the Voltage difference driving force of Potassium:

A

The electrical force will tend to direct positively charged ions (cations such as sodium, potassium, and calcium) to flow into a cel

36
Q

What are the source and evidence of Endolymph? (3)

A

Directly from perilymph, NOT blood

Evidence from experiments: Studying the K and Cl exchange

Different effects of K-free perfusion in perilymph spaces and blood vessels

37
Q

What is the role of Reissner’s membrane?

A

Little is known about transportation, certainly agree that there is certain amount of permeability to some ions.

38
Q

Where does the generation of potassium occur?

A

Occurs across Stria vascularis (StV) & EP generation

39
Q

What are the main point of potassium generation across the Stria Vascularis? (4)

A
40
Q

Explain the 4 key concepts of Davis Battery:

A
  • Also called variable resistance theory
  • Two batteries
    Big one at StV for EP
    Small one at HC membrane for intracellular potential
  • Two batteries are in serial connection with the variable resistance—MET channels
  • Standing current (without sound)
41
Q

What is standing current?

A

Current flow but with no sound stimulus

42
Q

What are the advantages of potassium as a carrier for transduction current? (3)

A
  1. Downward movement from endolymph to HC to perilymph (no immediate requirement for energy, reduce noise)
  2. Little disturbance of cytosolic homeostasis
  3. K+ channels on basal-lateral wall of OHCs provide transduction current and maintain resting potential
43
Q

Explain the bioengineering of the cochlea (4):

A
  • The major energy generation site (StV) 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

44
Q

Explain the bioengineering of the cochlea:

A
  • The major energy generation site (StV) 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

45
Q

Explain the bioengineering of the cochlea:

A
  • The major energy generation site (StV) 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

46
Q

Explain what is occurring in this picture:

A

Voltage is recorded when the electrode penetrates the lateral wall of the cochlea

The DC potential in marginal cell is 5-10 mV higher than that in SM

When the electrode enters into the MC there is a big jump and then when it gets into Scala Medius there is a slight drop

47
Q

Why are marginal cells special (3)?

A

Positive intracellular potentials compared to other cells

Concentration slightly higher than SM

EP generated in the Intrastrial Fluid

48
Q

Explain this image:

A

Easy pathway for potassium to move gap junction which explains why K comes from perilymph

49
Q

What are the important Ion channels for K transportation across StV? (3)

A
  • K diffusion channel on intermediate cells (KCNJ10)
  • Apical K channels on marginal cells (KCNQ1/KCNE1)
  • Na-2Cl-K co-transporter (SLC12A2)
50
Q

Explain the generation of the endocochlear potential through the channels: (3)

A
  • EP generated across KCNJ10 K channels
  • Marginal cells produce extremely low [K] in intrastrial space, where V= 90 mV
  • Facilitating K diffusion through KCNJ10 K channels to generate EP
51
Q

What is the evidence for KCNJ10 K channel:

A
52
Q

What is the evidence for the KCNJ10 K channel generating EP? (4)

A
  • EP is found across basal cell barrier
  • Intermediate cells have gap-junction with basal cell as K pathway to StV
  • K equilibrium voltage across IC is 120 mV, favor K moving out of IC to intrastria space
  • Data from channel manipulation: blockers, gene knockout etc. Dysfunction of KCNJ10 K
53
Q

What is the role of marginal cells? (5)

A
  • 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
54
Q

Explain the main points of the K recycling from perilymph to stria vacularis: (6)

A
  1. From endolymph to SV and ST and then strial vascularis, not to blood
  2. Recycling via supporting cells in OC and around spiral ligament,
  3. Fibrocytes at spiral prominence involved
  4. gap-junction: easy pathway
  5. Claudius cells are bridge between endolymph and intrastria space, contacting fibrocytes
  6. Fibrocytes have gap junction with basal cells of stria vascularis
55
Q

The gap junction is connected to:

A

Intercellular connection, directly connect cytoplasm

56
Q

What are the Gap Junction Functions? (4)

A

Electrical and metabolic coupling
Tumor suppressor
Adhesive function
Carboxyl-terminal in signaling cytoplasmic pathways

57
Q

Explain the pathway of the Gap Junction:

A

HC – (or Perilymph then to ) Supporting Cells – Fybrocitis Gap junction- SM

58
Q

What is occurring in this image?

A

Summary of the movement of Potassium through the gap junction system HC – (or Perilymph then to ) Supporting Cells – Fybrocitis Gap junction- SM

59
Q

How many types of proteins/genes are there in the gap junction?

A

There are more than 22 types

60
Q

What are the dominant proteins of the gap junction in the cochlea? (2)

A

CX26 and CX30 dominant in cochleae

61
Q

What are the other important proteins of the gap junction in the cochlea? (3)

A

Cx29,31,43

62
Q

What gene is associated with the CX26 protein in the cochlea?

A

GJB2

63
Q

What gene is associated with the CX30 protein in the cochlea?

A

GJB6

64
Q

What does Cx stand for?

A

Connexin

65
Q

What is the main cause of genetic-related hearing loss?

A

Mutation of GJB2 and GJB6

66
Q

What TYPE of hearing loss does the mutation of GJB2 and GJB6 cause?

A

Type of hearing loss: autosomal non-syndromic, recessive

Prevalence: ~50% (in total of autosomal non-syndromic hearing loss), mainly GJB2

67
Q

What is the prevalence of hearing loss mainly related to GJB2?

A

~50% (in total of autosomal non-syndromic hearing loss), mainly GJB2

68
Q

What DEGREE of hearing loss from GJB2 and GJB6?

A

GJB2: profound at birth
GJB6: mild to moderate, progressive

69
Q

What is the carrier rate for each of the GJB2 and GJB6 mutations?

A

Carrier rate: 1-4% for GJB2 mutation, 1% for GJB6 mutation

70
Q

What is the difference between a heterozygote and a double heterozygote?

A

Heterozygote: Heterozygote in this this case is where the subject is a carrier of one of the genes, does not cause HL

Double heterozygote: Double Heterozygote means carries both genes which cause genetic HL

71
Q

What is the hypothesis associated with the Mechanisms of HL with Cx mutations?

A

The K+ recycling hypothesis:

  • Based upon the major function of Cx and the importance of this function in cochlear physiology
  • Lack of solid evidence that potassium recycling is breaken down after mutation
    Many HL-associated mutation of Cx26 does not disrupts K recycling
72
Q

What does this experiment show? (2)

A

If we target the KO of Cx26 in supporting cells it does not disrupt the permeability of the supporting cells

The result shows redundancy of the gap junction gene function: the gap junctions still exist and work after one gene knockout.

73
Q

Explain this graph:

A

If Cx26 is mutated later in development, HCs are okay.
There is no substantial HC loss in Cx26 deficiency-induced late-onset hearing loss

1 gene can code multiple proteins and play multiple functions

74
Q

What are the gap junction mechanisms?

A

Cx forms the gap junction

Congenital deafness with Cx mutation:
developmental disorders (Normal Cx function is required in the critical period for normal development).

Late-onset, progressive HL with Cx mutation: damage in active amplification.

75
Q

What are the reabsorption sites for perilymph?

A

below BM at the medial and lateral corner

CMSD5280 Audition ll (19 decks)

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