Few Ca<sub>V</sub>1.3 Channels Regulate the Exocytosis of a Synaptic Vesicle at the Hair Cell Ribbon Synapse

Brandt, Andreas; Khimich, Darina; Moser, Tobias

doi:10.1523/jneurosci.3411-05.2005

Cited by 284 publications

(477 citation statements)

References 47 publications

Supporting

Mentioning

431

Contrasting

Unclassified

Order By: Relevance

“…This effect has been partly attributed to elevated intracellular Ca 2ϩ from activation of the LTCC. In hippocampal and cerebellar Purkinjie neurons and some sensory neurons, LTCCs may also contribute to normal functions of neurotransmitter release (95)(96)(97)(98)(99). A slower deactivation LTCC tail current in the presenilin mutants during recovery from stress-inducing treatments will result in elevated Ca 2ϩ influx and increased release probability of synaptic vesicles, which is consistent with our observation of the increased EJC amplitude (Supplemental Fig.…”

Section: Discussionsupporting

confidence: 90%

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

et al. 2006

View full text Add to dashboard Cite

It has been shown that presenilin is involved in maintaining Ca 2؉ homeostasis in neurons, including regulating endoplasmic reticulum (ER) Ca 2؉ storage. From studies of primary cultures and cell lines, however, its role in stress-induced responses is still controversial. In the present study we analyzed the effects of presenilin mutations on membrane currents and synaptic functions in response to stress using an in vivo preparation. We examined voltage-gated K ؉ and Ca 2؉ currents at the Drosophila larval neuromuscular junction (NMJ) with voltage-clamp recordings. Our data showed that both currents were generally unaffected by loss-of-function or Alzheimer's disease (AD) -associated presenilin mutations under normal or stress conditions induced by heat shock (HS) or ER stress. In larvae expressing the mutant presenilins, prolonged Ca 2؉ tail current, reflecting slower deactivation kinetics of Ca 2؉ channels, was observed 1 day after stress treatments were terminated. It was further demonstrated that the L-type Ca 2؉ channel was specifically affected under these conditions. Moreover, synaptic plasticity at the NMJ was reduced in larvae expressing the mutant presenilins. At the behavioral level, memory in adult flies was impaired in the presenilin mutants 1 day after HS. The results show that presenilin function is important during the poststress period and its impairment contributes to memory dysfunction observed during adaptation to normal conditions after stress. Our findings suggest a new stress-related mechanism by which presenilin may be implicated in the neuropathology of

show abstract

Section: Discussionsupporting

confidence: 90%

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

et al. 2006

View full text Add to dashboard Cite

show abstract

“…3C) and 1.4 for the integral of the AF response (data not shown). A similar linear relation has been shown before at the hair cell synapse (11,(14)(15)(16) and explained by a ''nanodomain model,'' where opening of one Ca 2ϩ channel activates release of only very nearby vesicles (15,17). Thus, as open probability rises with depolarization, each Ca 2ϩ channel's ''cluster'' of vesicles sums to produce a linear dependence on Ca 2ϩ current.…”

Section: Resultssupporting

confidence: 76%

“…This relation is presumed to result from the cooperative binding of three to four Ca 2ϩ ions at the Ca 2ϩ sensor. Similarly, using Ca 2ϩ uncaging and IHC capacitance recordings, Beutner et al (28) found a fifth-order Ca 2ϩ dependence of release, and Brandt et al (15) reported a high apparent Ca 2ϩ cooperativity observed during changes of single channel currents and rapid flicker block. Our data also support the evolving picture that for the physiological relevant voltage range, hair cell synapses operate with a linear Ca 2ϩ dependence of release.…”

Section: Numbers Of Vesicles and Release Ratesmentioning

confidence: 94%

Time course and calcium dependence of transmitter release at a single ribbon synapse

Goutman

Glowatzki

2007

Proc. Natl. Acad. Sci. U.S.A.

223

322

View full text Add to dashboard Cite

At the first synapse in the auditory pathway, the receptor potential of mechanosensory hair cells is converted into a firing pattern in auditory nerve fibers. For the accurate coding of timing and intensity of sound signals, transmitter release at this synapse must occur with the highest precision. To measure directly the transfer characteristics of the hair cell afferent synapse, we implemented simultaneous whole-cell recordings from mammalian inner hair cells (IHCs) and auditory nerve fiber terminals that typically receive input from a single ribbon synapse. During a 1-s IHC depolarization, the synaptic response depressed >90%, representing the main source for adaptation in the auditory nerve. Synaptic depression was slightly affected by ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization; however, it was mostly caused by reduced vesicular release. When the transfer function between transmitter release and Ca 2؉ influx was tested at constant open probability for Ca 2؉ channels (potentials >0 mV), a super linear relation was found. This relation is presumed to result from the cooperative binding of three to four Ca 2؉ ions at the Ca 2؉ sensor. However, in the physiological range for receptor potentials (؊50 to ؊30 mV), the relation between Ca 2؉ influx and afferent activity was linear, assuring minimal distortion in the coding of sound intensity. Changes in Ca 2؉ influx caused an increase in release probability, but not in the average size of multivesicular synaptic events. By varying Ca 2؉ buffering in the IHC, we further investigate how Ca 2؉ channel and Ca 2؉ sensor at this synapse might relate.hearing ͉ exocytosis ͉ hair cell ͉ synaptic transmission ͉ auditory nerve fiber M echanosensory hair cells of the inner ear release neurotransmitter continuously and with high temporal precision onto dendrites of auditory nerve fibers (AFs) (1); therefore, availability of releasable synaptic vesicles is critical. Synaptic ribbons, presynaptic structures presenting a halo of tethered vesicles, also found in retinal photoreceptors and bipolar cells (2), are thought to facilitate accumulation of vesicles presynaptically (3). Postsynaptically, ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors mediate fast synaptic transmission (4). The response of the cochlea to sound has been investigated in great detail: prolonged sound stimulation produces an increase in the firing activity of the auditory nerve that adapts on a milliseconds time scale (5). However, direct demonstration of the synaptic processes underlying adaptation and sustained release is still missing. Heretofore, hair cell exocytosis has been measured by changes in membrane capacitance that sum activity from all of the dozens of ribbon synapses in each cell (3). Capacitance measurements therefore cannot distinguish properties of individual ribbons and are limited in temporal resolution, requiring extrapolation for the earliest components. Nor does this approach reveal what role postsynaptic desensitization might play.I...

show abstract

“…Such pooling does not take into account natural cell heterogeneity, but assumes that cells are identical. In another approach, data recorded from all cells have been used to investigate the relation between ∆C m and Q (Brandt et al, 2005), but this analysis neglects that data from different depolarizations applied to the same cell are more strongly correlated than data obtained in different cells, and is likely to overstate the statistical significance of regression coefficients (Venables and Ripley, 2002).…”

Section: Mixed-effects Analysis Of Exocytosis In Mouse β-Cellsmentioning

confidence: 99%

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Pedersen

Cortese

Eliasson

2011

Progress in Biophysics and Molecular Biology

View full text Add to dashboard Cite

Few Ca_V1.3 Channels Regulate the Exocytosis of a Synaptic Vesicle at the Hair Cell Ribbon Synapse

Cited by 284 publications

References 47 publications

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Time course and calcium dependence of transmitter release at a single ribbon synapse

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Contact Info

Product

Resources

About

Few CaV1.3 Channels Regulate the Exocytosis of a Synaptic Vesicle at the Hair Cell Ribbon Synapse

Cited by 284 publications

References 47 publications

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons

Time course and calcium dependence of transmitter release at a single ribbon synapse

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Contact Info

Product

Resources

About

Few Ca_V1.3 Channels Regulate the Exocytosis of a Synaptic Vesicle at the Hair Cell Ribbon Synapse