Hair Cells

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Hair Cells

• Vestibular Classics
• February 2, 2007
• Isabel Acevedo

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Why hair cells?

• Sensory receptors of the vestibular and auditory
  systems in all vertebrates.
• Transduces mechanical stimuli into biological
  signals that are presented to the brain by
  afferents.

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Hair Cell Morphology
Cuticular Plate
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Hair Cell Morphology

• Types of Links
• Kinocilial Links (KL)
• Ankle Links (AL)
• Shaft Links (SL)
• Upper Lateral Links (UL)
• Tip Links (TL)

TL
AL SL
Adapted from Pickles Corey 1992
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Stereocilia Growth
1st Step Stereocilia appear to elongate
2nd Step Stereocilia increase in width
3st Step Stereocilia increase in length
Tilney et al, 1986.
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Hair Cell Types
Dickman in Fundamental Neuroscience, 2nd ed.
(2002)
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Hair Cell Communication

• Afferent Innervation heterogenous population of
  fibers, whose somata are located in Scarpas
  ganglion, that convey hair cell response to the
  brainstem cerebrum. Excitatory amino acids
  such as aspartate glutamate are the
  neurotransmitters at the synapse between the
  receptor cell afferent fibers
• Efferent Innervation fibers originating in the
  medulla, at the level of the vestibular nuclei,
  that control the activity of hair cells. These
  fibers contain acetylcholine and calcitonine gene
  as neurotransmitters and are activated by
  behaviorally arousing stimuli or by trigeminal
  stimulation.

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Accessory Structures
Otolith Organs Linear Accelerations
Semicircular Canals Angular Acceleration
Dickman in Fundamental Neuroscience, 2nd ed.
(2002)
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Transduction

• Conversion of mechanical energy into electrical
  charges.
• External mechanical stimulus causes hair cells to
  move
• Appropriate mechanical stimulus modulates an
  ionic current flow from endolymph into apical end.

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Transduction In Vitro
Hudspeth Corey 1977
Dickman in Fundamental Neuroscience, 2nd ed.
(2002)
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Transduction In Vitro
Hudspeth and Corey, 1977
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Transduction In Vivo
Ionic Composition of Fluids
Dickman in Fundamental Neuroscience, 2nd ed.
(2002)
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Transduction Negative Feedback
Release neurotransmitters (Asp Glu)
?Ki
?Ca2i
?Ki
Mechanical stimulus towards kinocilium
Depolarization
Activate voltage-gated Ca2 channels
Ca2 activated K (BK) channels
Fettiplace Fuch, 1999.
High Intensity
Low Intensity
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Transduction Calcium Channels

• Two types of Ca2 buffers.
• Immobile buffers (pumps exchangers) slow
  release of Ca2 into the presynaptic cytoplasm.
• Mobile buffer (Ca2 binding proteins like
  calbindin-D28k) cause presynaptic Ca2i to
  fall very quickly by sequestering nearly all free
  Ca2 within 100 µs after Ca2 channels close.

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Gating Springs
Pickles Corey, 1992.
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Gating Springs
Lenzi Roberts, 1994.
Pickles Corey, 1992.
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Adaptation

• Hair bundle is unlikely to develop so accurately
  that the sensitive transduction apparatus is
  perfectly poised at is position of greatest
  mechanosensitivity.
• Necessary mechanism to compensate for
  developmental irregularities and environmental
  changes adjust the tension at the gating
  springs.
• If tip links are the gating springs, the most
  likely possibility is that the anchoring points
  are repositioned.
• Depends on Ca2i.

Pickles Corey, 1992.
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Site of Transduction

• Hudspeth Extracellular potential change was
  greatest around the top of the bundle.
• Ca2-sensitive fluorescent dye Large
  fluorescence signals observed in the apical
  cytoplasm, immediately beneath the hair bundle.

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Morphologic Polarization
Zakir, et al., 2002
Dickman in Fundamental Neuroscience, 2nd ed.
(2002)
Si, et al., 2002
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Regeneration
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Summary

• Hair Cells are the receptors of mechanical
  stimuli.
• Hair cells transduce mechanical stimuli to be
  presented to and analyzed by the brain.
• Hair Cells are heterogeneous agencies of
  transduction by virtue of their morphological
  and physiological differences varying
  complements of the transmitters and modulators
  and their receptors and by the possibility that
  they behave differently in regard to resting and
  stimulated modes and adapt differently.