Transcript Hair Cells - Radboud Universiteit

Hair Cells
Vestibular Classics
February 2, 2007
Isabel Acevedo
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.
Hair Cell Morphology
Cuticular Plate
Hair Cell Morphology
Types of Links:
Kinocilial Links (KL)
Ankle Links (AL)
Shaft Links (SL)
Upper Lateral Links (UL)
Tip Links (TL)
TL
Adapted from Pickles & Corey 1992
AL & SL
Stereocilia Growth
1st Step:
Stereocilia appear to
elongate
2nd Step:
Stereocilia increase in
width
3st Step:
Stereocilia increase in
length
Tilney et al, 1986.
Hair Cell Types
Dickman in Fundamental Neuroscience, 2nd ed. (2002)
Hair Cell Communication
Afferent Innervation: heterogenous population of fibers,
whose somata are located in Scarpa’s 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.
Accessory Structures
Semicircular Canals
Otolith Organs
Angular Acceleration
Linear Accelerations
Dickman in Fundamental Neuroscience, 2nd ed. (2002)
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.
Transduction: In Vitro
Hudspeth & Corey 1977
Dickman in Fundamental Neuroscience, 2nd ed. (2002)
Transduction: In Vitro
Hudspeth and Corey, 1977
Transduction: In Vivo
Ionic Composition of Fluids
ION
Perilymph
Endolymph
Sodium (mM)
141
1.3
Potassium (mM)
6
157
Chloride (mM)
121
132
Bicarbonate
(mM)
18
31
Calcium (mM)
0.6
0.0023
Dickman in Fundamental Neuroscience, 2nd ed. (2002)
Transduction: Negative Feedback
Release neurotransmitters
(Asp & Glu)
Mechanical
stimulus towards
kinocilium
↑[K+]
i
Depolarization
↓[K+]i
↑[Ca2+]i
Activate voltage-gated
Ca2+ channels
Ca2+ activated K+
(BK) channels
Fettiplace & Fuch, 1999.
Low Intensity
High Intensity
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 [Ca2+]i to
fall very quickly by sequestering nearly all free
Ca2+ within 100 μs after Ca2+ channels close.
Gating Springs
Pickles & Corey, 1992.
Gating Springs
Pickles & Corey, 1992.
Lenzi & Roberts, 1994.
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 [Ca2+]i.
Pickles & Corey, 1992.
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.
Morphologic Polarization
Zakir, et al., 2002
Dickman in Fundamental Neuroscience, 2nd ed. (2002)
Si, et al., 2002
Regeneration
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.