Proton-mediated block of Ca2+ channels during multivesicular release regulates short-term plasticity at an auditory hair cell synapse

Soyoun Cho, Henrique von Gersdorff

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+ channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological, in vivo-like holding potentials (Vh = —60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+ currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked at Vh = — 90 mV due to the presence of a T-type Ca2+ current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+ buffer (10 mM BAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+ current. We estimate that this transient block is due to the rapid multivesicular release of ~ 600 -1300 H+ ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mM HEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+ current leads to more efficient exocytosis per Ca2+ ion influx and it may contribute to spike adaptation at the auditory nerve.

Original languageEnglish (US)
Pages (from-to)15877-15887
Number of pages11
JournalJournal of Neuroscience
Volume34
Issue number48
DOIs
StatePublished - Nov 26 2014

Fingerprint

Auditory Hair Cells
Exocytosis
Synapses
Protons
HEPES
Buffers
Ions
Rana catesbeiana
Cochlear Nerve
Synaptic Vesicles
Bicarbonates
Neurotransmitter Agents
Glutamic Acid

Keywords

  • Auditory
  • Calcium current
  • Electrophysiology
  • Exocytosis
  • Hair cells
  • Protons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Proton-mediated block of Ca2+ channels during multivesicular release regulates short-term plasticity at an auditory hair cell synapse. / Cho, Soyoun; von Gersdorff, Henrique.

In: Journal of Neuroscience, Vol. 34, No. 48, 26.11.2014, p. 15877-15887.

Research output: Contribution to journalArticle

@article{282ee7e5916548b4a4b9b9fa07ed5d2b,
title = "Proton-mediated block of Ca2+ channels during multivesicular release regulates short-term plasticity at an auditory hair cell synapse",
abstract = "Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+ channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological, in vivo-like holding potentials (Vh = —60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+ currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked at Vh = — 90 mV due to the presence of a T-type Ca2+ current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+ buffer (10 mM BAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+ current. We estimate that this transient block is due to the rapid multivesicular release of ~ 600 -1300 H+ ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mM HEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+ current leads to more efficient exocytosis per Ca2+ ion influx and it may contribute to spike adaptation at the auditory nerve.",
keywords = "Auditory, Calcium current, Electrophysiology, Exocytosis, Hair cells, Protons",
author = "Soyoun Cho and {von Gersdorff}, Henrique",
year = "2014",
month = "11",
day = "26",
doi = "10.1523/JNEUROSCI.2304-14.2014",
language = "English (US)",
volume = "34",
pages = "15877--15887",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "48",

}

TY - JOUR

T1 - Proton-mediated block of Ca2+ channels during multivesicular release regulates short-term plasticity at an auditory hair cell synapse

AU - Cho, Soyoun

AU - von Gersdorff, Henrique

PY - 2014/11/26

Y1 - 2014/11/26

N2 - Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+ channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological, in vivo-like holding potentials (Vh = —60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+ currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked at Vh = — 90 mV due to the presence of a T-type Ca2+ current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+ buffer (10 mM BAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+ current. We estimate that this transient block is due to the rapid multivesicular release of ~ 600 -1300 H+ ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mM HEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+ current leads to more efficient exocytosis per Ca2+ ion influx and it may contribute to spike adaptation at the auditory nerve.

AB - Synaptic vesicles release both neurotransmitter and protons during exocytosis, which may result in a transient acidification of the synaptic cleft that can block Ca2+ channels located close to the sites of exocytosis. Evidence for this effect has been reported for retinal ribbon-type synapses, but not for hair cell ribbon synapses. Here, we report evidence for proton release from bullfrog auditory hair cells when they are held at more physiological, in vivo-like holding potentials (Vh = —60 mV) that facilitate multivesicular release. During paired recordings of hair cells and afferent fibers, L-type voltage-gated Ca2+ currents showed a transient block, which was highly correlated with the EPSC amplitude (or the amount of glutamate release). This effect was masked at Vh = — 90 mV due to the presence of a T-type Ca2+ current and blocked by strong pH buffering with HEPES or TABS. Increasing vesicular pH with internal methylamine in hair cells also abolished the transient block. High concentrations of intracellular Ca2+ buffer (10 mM BAPTA) greatly reduced exocytosis and abolished the transient block of the Ca2+ current. We estimate that this transient block is due to the rapid multivesicular release of ~ 600 -1300 H+ ions per synaptic ribbon. Finally, during a train of depolarizing pulses, paired pulse plasticity was significantly changed by using 40 mM HEPES in addition to bicarbonate buffer. We propose that this transient block of Ca2+ current leads to more efficient exocytosis per Ca2+ ion influx and it may contribute to spike adaptation at the auditory nerve.

KW - Auditory

KW - Calcium current

KW - Electrophysiology

KW - Exocytosis

KW - Hair cells

KW - Protons

UR - http://www.scopus.com/inward/record.url?scp=84911909031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911909031&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2304-14.2014

DO - 10.1523/JNEUROSCI.2304-14.2014

M3 - Article

C2 - 25429130

AN - SCOPUS:84911909031

VL - 34

SP - 15877

EP - 15887

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 48

ER -