Developmental Changes in Two Voltage-Dependent Sodium Currents in Utricular Hair Cells

Wooltorton, Julian R. A.; Gaboyard, Sophie; Hurley, Karen M.; Price, Steven D.; Garcia, Jasmine L.; Zhong, Meng; Lysakowski, Anna; Eatock, Ruth Anne

doi:10.1152/jn.00649.2006

Cited by 58 publications

(125 citation statements)

References 104 publications

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“…We did not see the mixed Ca 2+ -Na + spikes that are typical of mouse IHCs in the first postnatal week (Marcotti et al, 2003b). All Atoh1 + cells lacked the voltage-gated Na + currents of immature HC subtypes (Chabbert et al, 2003;Eckrich et al, 2012;Géléoc et al, 2004;Li et al, 2010;Marcotti et al, 2003b;Oliver et al, 1997;Witt et al, 1994;Wooltorton et al, 2007). Again, these channels either were never expressed or had stopped being expressed by the earliest time point we examined, 12 days of in vitro differentiation.…”

Section: Voltage-gated Currents In Differentiated Hair Cell-like Cellsmentioning

confidence: 73%

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

McLean

Eatock

et al. 2016

Development

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Disorders of hearing and balance are most commonly associated with damage to cochlear and vestibular hair cells or neurons. Although these cells are not capable of spontaneous regeneration, progenitor cells in the hearing and balance organs of the neonatal mammalian inner ear have the capacity to generate new hair cells after damage. To investigate whether these cells are restricted in their differentiation capacity, we assessed the phenotypes of differentiated progenitor cells isolated from three compartments of the mouse inner ear -the vestibular and cochlear sensory epithelia and the spiral ganglion -by measuring electrophysiological properties and gene expression. Lgr5 + progenitor cells from the sensory epithelia gave rise to hair cell-like cells, but not neurons or glial cells. Newly created hair cell-like cells had hair bundle proteins, synaptic proteins and membrane proteins characteristic of the compartment of origin. PLP1 + glial cells from the spiral ganglion were identified as neural progenitors, which gave rise to neurons, astrocytes and oligodendrocytes, but not hair cells. Thus, distinct progenitor populations from the neonatal inner ear differentiate to cell types associated with their organ of origin.

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Section: Voltage-gated Currents In Differentiated Hair Cell-like Cellsmentioning

confidence: 73%

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

McLean

Eatock

et al. 2016

Development

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“…Previously, SCN2A and SCNA3A were suggested as candidate genes for deafness at the DFNA16 locus; the evidence, however, is inconclusive (Kasai et al 2001). In addition, both Nav1.2 (SCN2A) and Nav1.6 (SCN8A) were identified using single cell RT-PCR on rat utricular hair cells (Chabbert et al 2003), while Nav1.5 (SCN5A) was reported recently using electrophysiology, RT-PCR, and immunolocalization (Wooltorton et al 2007). …”

Section: K+ Channelsmentioning

confidence: 99%

Ion Channel Gene Expression in the Inner Ear

Gabashvili

Sokolowski

Morton

et al. 2007

JARO

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The ion channel genome is still being defined despite numerous publications on the subject. The ion channel transcriptome is even more difficult to assess. Using high-throughput computational tools, we surveyed all available inner ear cDNA libraries to identify genes coding for ion channels. We mapped over 100,000 expressed sequence tags (ESTs) derived from human cochlea, mouse organ of Corti, mouse and zebrafish inner ear, and rat vestibular end organs to Homo sapiens, Mus musculus, Danio rerio, and Rattus norvegicus genomes. A survey of EST data alone reveals that at least a third of the ion channel genome is expressed in the inner ear, with highest expression occurring in hair cell-enriched mouse organ of Corti and rat vestibule. Our data and comparisons with other experimental techniques that measure gene expression show that every method has its limitations and does not per se provide a complete coverage of the inner ear ion channelome. In addition, the data show that most genes produce alternative transcripts with the same spectrum across multiple organisms, no ion channel gene variants are unique to the inner ear, and many splice variants have yet to be annotated. Our high-throughput approach offers a qualitative computational and experimental analysis of ion channel genes in inner ear cDNA collections. A lack of data and incomplete gene annotations prevent both rigorous statistical analyses and comparisons of entire ion channelomes derived from different tissues and organisms.

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“…In rodents, calyx terminals appear during the first postnatal week when ion channel complements in hair cells and postnatal afferents may change rapidly (Rüsch et al 1998;Hurley et al 2006;Wooltorton et al 2007). K + currents in vestibular ganglion cells have been studied during the early postnatal period (P0-P8) in mouse (Chabbert et al 2001;Risner and Holt 2006).…”

Section: Comparison To Preparations Studied During Postnatal Developmentmentioning

confidence: 99%

K+ Currents in Isolated Vestibular Afferent Calyx Terminals

Dhawan

Mann

Meredith

et al. 2010

JARO

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Vestibular hair cells transduce mechanical displacements of their hair bundles into an electrical receptor potential which modulates transmitter release and subsequent action potential firing in afferent neurons. To probe ionic mechanisms underlying sensory coding in vestibular calyces, we used the whole-cell patch-clamp technique to record action potentials and K + currents from afferent calyx terminals isolated from the semicircular canals of Mongolian gerbils. Calyx terminals showed minimal current at the mean zero-current potential (−60 mV), but two types of outward K + currents were identified at potentials above −50 mV. The first current was a rapidly activating and inactivating K + current that was blocked by 4-aminopyridine (4-AP, 2.5 mM) and BDS-I (up to 250 nM). The time constant for activation of this current decreased with membrane depolarization to a minimum value of ∼1 ms. The 4-AP-sensitive current showed steady-state inactivation with a half-inactivation of approximately −70 mV. A second, more slowly activating current (activation time constant was 8.5±0.7 ms at −8 mV) was sensitive to TEA (30 mM). The TEA-sensitive current also showed steady-state inactivation with a half-inactivation of −95.4±1.4 mV, following 500-ms duration conditioning pulses. A combination of 4-AP and TEA blocked ∼90% of the total outward current.In current clamp, single Na + -dependent action potentials were evoked following hyperpolarization to potentials more negative than the resting potential. 4-AP application increased action potential width, whereas TEA both increased the width and greatly reduced repolarization of the action potential.

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Developmental Changes in Two Voltage-Dependent Sodium Currents in Utricular Hair Cells

Cited by 58 publications

References 104 publications

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

Ion Channel Gene Expression in the Inner Ear

K+ Currents in Isolated Vestibular Afferent Calyx Terminals

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