gemini Encodes a Zebrafish L-Type Calcium Channel That Localizes at Sensory Hair Cell Ribbon Synapses

Samuel Sidi, Elisabeth Busch-Nentwich, Rainer Friedrich, Ulrike Schoenberger, Teresa Nicolson

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC encoding gene, cav1.3a, underlie the auditory-vestibular defects of gemini (gem) circler mutants. gem homozygous receptor mutant HCs display normal cell viability, afferent synaptogenesis, and peripheral innervation, yet exhibit strongly reduced extracellular potentials (∼50% of wild-type potentials). Apical FM1-43 uptake, however, is unaffected in gem mutant HCs, suggesting that mechanotransduction channels are functional. Using a Gem-specific antibody, we show that the bulk of Gem/Cav1.3a immunoreactivity in HCs is restricted to basally located focal spots. The number and location of focal spots relative to nerve terminals, and their remarkable ring-shaped structure, which is reminiscent of synaptic dense bodies, are consistent with Gem/Ca v1.3a channels clustering at HC ribbon synapses.

Original languageEnglish (US)
Pages (from-to)4213-4223
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number17
DOIs
StatePublished - Apr 28 2004

Fingerprint

L-Type Calcium Channels
Zebrafish
Synapses
Inner Auditory Hair Cells
Inner Ear
Neurotransmitter Agents
Cluster Analysis
Vertebrates
Organism Cloning
Cell Survival
Mutation
Antibodies
Genes

Keywords

  • Deafness
  • Gemini
  • Hair cell
  • L-type calcium channels
  • Microphonics
  • Ribbon synapse
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

gemini Encodes a Zebrafish L-Type Calcium Channel That Localizes at Sensory Hair Cell Ribbon Synapses. / Sidi, Samuel; Busch-Nentwich, Elisabeth; Friedrich, Rainer; Schoenberger, Ulrike; Nicolson, Teresa.

In: Journal of Neuroscience, Vol. 24, No. 17, 28.04.2004, p. 4213-4223.

Research output: Contribution to journalArticle

Sidi, Samuel ; Busch-Nentwich, Elisabeth ; Friedrich, Rainer ; Schoenberger, Ulrike ; Nicolson, Teresa. / gemini Encodes a Zebrafish L-Type Calcium Channel That Localizes at Sensory Hair Cell Ribbon Synapses. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 17. pp. 4213-4223.
@article{afdbea44edc54ac7b4fd36a71d2178b2,
title = "gemini Encodes a Zebrafish L-Type Calcium Channel That Localizes at Sensory Hair Cell Ribbon Synapses",
abstract = "L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC encoding gene, cav1.3a, underlie the auditory-vestibular defects of gemini (gem) circler mutants. gem homozygous receptor mutant HCs display normal cell viability, afferent synaptogenesis, and peripheral innervation, yet exhibit strongly reduced extracellular potentials (∼50{\%} of wild-type potentials). Apical FM1-43 uptake, however, is unaffected in gem mutant HCs, suggesting that mechanotransduction channels are functional. Using a Gem-specific antibody, we show that the bulk of Gem/Cav1.3a immunoreactivity in HCs is restricted to basally located focal spots. The number and location of focal spots relative to nerve terminals, and their remarkable ring-shaped structure, which is reminiscent of synaptic dense bodies, are consistent with Gem/Ca v1.3a channels clustering at HC ribbon synapses.",
keywords = "Deafness, Gemini, Hair cell, L-type calcium channels, Microphonics, Ribbon synapse, Synaptic transmission",
author = "Samuel Sidi and Elisabeth Busch-Nentwich and Rainer Friedrich and Ulrike Schoenberger and Teresa Nicolson",
year = "2004",
month = "4",
day = "28",
doi = "10.1523/JNEUROSCI.0223-04.2004",
language = "English (US)",
volume = "24",
pages = "4213--4223",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "17",

}

TY - JOUR

T1 - gemini Encodes a Zebrafish L-Type Calcium Channel That Localizes at Sensory Hair Cell Ribbon Synapses

AU - Sidi, Samuel

AU - Busch-Nentwich, Elisabeth

AU - Friedrich, Rainer

AU - Schoenberger, Ulrike

AU - Nicolson, Teresa

PY - 2004/4/28

Y1 - 2004/4/28

N2 - L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC encoding gene, cav1.3a, underlie the auditory-vestibular defects of gemini (gem) circler mutants. gem homozygous receptor mutant HCs display normal cell viability, afferent synaptogenesis, and peripheral innervation, yet exhibit strongly reduced extracellular potentials (∼50% of wild-type potentials). Apical FM1-43 uptake, however, is unaffected in gem mutant HCs, suggesting that mechanotransduction channels are functional. Using a Gem-specific antibody, we show that the bulk of Gem/Cav1.3a immunoreactivity in HCs is restricted to basally located focal spots. The number and location of focal spots relative to nerve terminals, and their remarkable ring-shaped structure, which is reminiscent of synaptic dense bodies, are consistent with Gem/Ca v1.3a channels clustering at HC ribbon synapses.

AB - L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC encoding gene, cav1.3a, underlie the auditory-vestibular defects of gemini (gem) circler mutants. gem homozygous receptor mutant HCs display normal cell viability, afferent synaptogenesis, and peripheral innervation, yet exhibit strongly reduced extracellular potentials (∼50% of wild-type potentials). Apical FM1-43 uptake, however, is unaffected in gem mutant HCs, suggesting that mechanotransduction channels are functional. Using a Gem-specific antibody, we show that the bulk of Gem/Cav1.3a immunoreactivity in HCs is restricted to basally located focal spots. The number and location of focal spots relative to nerve terminals, and their remarkable ring-shaped structure, which is reminiscent of synaptic dense bodies, are consistent with Gem/Ca v1.3a channels clustering at HC ribbon synapses.

KW - Deafness

KW - Gemini

KW - Hair cell

KW - L-type calcium channels

KW - Microphonics

KW - Ribbon synapse

KW - Synaptic transmission

UR - http://www.scopus.com/inward/record.url?scp=2442444290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442444290&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0223-04.2004

DO - 10.1523/JNEUROSCI.0223-04.2004

M3 - Article

C2 - 15115817

AN - SCOPUS:2442444290

VL - 24

SP - 4213

EP - 4223

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 17

ER -