Hair CellsHair Cells

Vestibular ClassicsVestibular Classics

February 2, 2007February 2, 2007

Isabel AcevedoIsabel Acevedo

Why hair cells?Why hair cells?

Sensory receptors of the Sensory receptors of the vestibular and auditory vestibular and auditory systems in all vertebrates.systems in all vertebrates.

Transduces mechanical Transduces mechanical stimuli into biological stimuli into biological signals that are presented signals that are presented to the brain by afferents.to the brain by afferents.

Hair Cell MorphologyHair Cell Morphology

Cuticular Plate

Hair Cell MorphologyHair Cell Morphology

Adapted from Pickles & Corey 1992

TL

Types of Links:

Kinocilial Links (KL)

Ankle Links (AL)

Shaft Links (SL)

Upper Lateral Links (UL)

Tip Links (TL)

AL & SL

Stereocilia GrowthStereocilia Growth1st Step:

Stereocilia appear to elongate

2nd Step:

Stereocilia increase in width

3st Step:

Stereocilia increase in length

Tilney et al, 1986.

Hair Cell TypesHair Cell Types

Dickman in Fundamental Neuroscience, 2nd ed. (2002)

Hair Cell CommunicationHair Cell Communication

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

Accessory StructuresAccessory Structures

Semicircular Canals

Angular Acceleration

Otolith Organs

Linear Accelerations

Dickman in Fundamental Neuroscience, 2nd ed. (2002)

TransductionTransduction

Conversion of mechanical energy into Conversion of mechanical energy into electrical charges.electrical charges.– External mechanical stimulus causes hair External mechanical stimulus causes hair

cells to movecells to move– Appropriate mechanical stimulus modulates Appropriate mechanical stimulus modulates

an ionic current flow from endolymph into an ionic current flow from endolymph into apical end.apical end.

Transduction: In VitroTransduction: In Vitro

Hudspeth & Corey 1977 Dickman in Fundamental Neuroscience, 2nd ed. (2002)

Transduction: In VitroTransduction: In Vitro

Hudspeth and Corey, 1977

Transduction: In VivoTransduction: In Vivo

IONION PerilymphPerilymph EndolymphEndolymph

Sodium (mM)Sodium (mM) 141141 1.31.3

Potassium (mM)Potassium (mM) 66 157157

Chloride (mM)Chloride (mM) 121121 132132

Bicarbonate Bicarbonate (mM)(mM)

1818 3131

Calcium (mM)Calcium (mM) 0.60.6 0.00230.0023

Ionic Composition of Fluids

Dickman in Fundamental Neuroscience, 2nd ed. (2002)

Transduction: Negative FeedbackTransduction: Negative Feedback

Mechanical stimulus towards

kinocilium

↑[K+]i

Depolarization

↑[Ca2+]i

Activate voltage-gated Ca2+ channels

↓[K+]i

Ca2+ activated K+ (BK) channels

Release neurotransmitters

(Asp & Glu)

Low Intensity High Intensity

Fettiplace & Fuch, 1999.

Transduction: Calcium ChannelsTransduction: Calcium Channels

Two types of CaTwo types of Ca2+2+ buffers. buffers.– Immobile buffers (pumps & exchangers): Immobile buffers (pumps & exchangers):

slow release of Caslow release of Ca2+2+ into the presynaptic into the presynaptic cytoplasm. cytoplasm.

– Mobile buffer (CaMobile buffer (Ca2+2+ binding proteins like binding proteins like calbindin-Dcalbindin-D28k28k): cause presynaptic [Ca): cause presynaptic [Ca2+2+]]i i to to

fall very quickly by sequestering nearly all free fall very quickly by sequestering nearly all free CaCa2+2+ within 100 within 100 μμs after Cas after Ca2+2+ channels close. channels close.

Gating SpringsGating Springs

Pickles & Corey, 1992.

Gating SpringsGating Springs

Lenzi & Roberts, 1994.Pickles & Corey, 1992.

AdaptationAdaptation

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

Depends on [CaDepends on [Ca2+2+]]ii..

Pickles & Corey, 1992.

Site of TransductionSite of Transduction

Hudspeth: Extracellular potential change Hudspeth: Extracellular potential change was greatest around the top of the bundle.was greatest around the top of the bundle.

CaCa2+2+-sensitive fluorescent dye: Large -sensitive fluorescent dye: Large fluorescence signals observed in the fluorescence signals observed in the apical cytoplasm, immediately beneath the apical cytoplasm, immediately beneath the hair bundle.hair bundle.

Morphologic PolarizationMorphologic Polarization

Dickman in Fundamental Neuroscience, 2nd ed. (2002)

Zakir, et al., 2002

Si, et al., 2002

RegenerationRegeneration

SummarySummary

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