Dataset Information

Alpha-Latrotoxin releases calcium in frog motor nerve terminals.

ABSTRACT: alpha-Latrotoxin (alpha-LTX) is a neurotoxin that accelerates spontaneous exocytosis independently of extracellular Ca(2+). Although alpha-LTX increases spontaneous transmitter release at synapses, the mechanism is unknown. We tested the hypothesis that alpha-LTX causes transmitter release by mobilizing intracellular Ca(2+) in frog motor nerve terminals. Transmitter release was measured electrophysiologically and with the vesicle marker FM1-43; presynaptic ion concentration dynamics were measured with fluorescent ion-imaging techniques. We report that alpha-LTX increases transmitter release after release of a physiologically relevant concentration of intracellular Ca(2+). Neither the blockade of Ca(2+) release nor the depletion of Ca(2+) from endoplasmic reticulum affected Ca(2+) signals produced by alpha-LTX. The Ca(2+) source is likely to be mitochondria, because the effects on Ca(2+) mobilization of CCCP (which depletes mitochondrial Ca(2+)) and of alpha-LTX are mutually occlusive. The release of mitochondrial Ca(2+) is partially attributable to an increase in intracellular Na(+), suggesting that the mitochondrial Na(+)/Ca(2+) exchanger is activated. Effects of alpha-LTX were not blocked when Ca(2+) increases were reduced greatly in saline lacking both Na(+) and Ca(2+) and by application of intracellular Ca(2+) chelators. Therefore, although increases in intracellular Ca(2+) may facilitate the effects of alpha-LTX on transmitter release, these increases do not appear to be necessary. The results show that investigations of Ca(2+)-independent alpha-LTX mechanisms or uses of alpha-LTX to probe exocytosis mechanisms would be complicated by the release of intracellular Ca(2+), which itself can trigger exocytosis.

SUBMITTER: Tsang CW

PROVIDER: S-EPMC6773046 | biostudies-literature | 2000 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

alpha-Latrotoxin releases calcium in frog motor nerve terminals.

Tsang C W CW Elrick D B DB Charlton M P MP

The Journal of neuroscience : the official journal of the Society for Neuroscience 20001201 23

alpha-Latrotoxin (alpha-LTX) is a neurotoxin that accelerates spontaneous exocytosis independently of extracellular Ca(2+). Although alpha-LTX increases spontaneous transmitter release at synapses, the mechanism is unknown. We tested the hypothesis that alpha-LTX causes transmitter release by mobilizing intracellular Ca(2+) in frog motor nerve terminals. Transmitter release was measured electrophysiologically and with the vesicle marker FM1-43; presynaptic ion concentration dynamics were measure ...[more]

PMID: 11102474

Similar Datasets

Project description:BackgroundNerve terminal invasion by an axonal spike activates voltage-gated channels, triggering calcium entry, vesicle fusion, and release of neurotransmitter. Ion channels activated at the terminal shape the presynaptic spike and so regulate the magnitude and duration of calcium entry. Consequently characterization of the functional properties of ion channels at nerve terminals is crucial to understand the regulation of transmitter release. Direct recordings from small neocortical nerve terminals have revealed that external [Ca(2+)] ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify the first component in a presynaptic calcium signaling pathway.Methodology/principal findingsBy combining genetic and pharmacological approaches with direct patch-clamp recordings from small acutely isolated neocortical nerve terminals we identify the extracellular calcium sensor. Our results show that the calcium-sensing receptor (CaSR), a previously identified G-protein coupled receptor that is the mainstay in serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist, reduced NSCC currents in direct terminal recordings in a dose-dependent and reversible manner. In contrast, glutamate and GABA did not affect the NSCC currents.Conclusions/significanceOur experiments identify CaSR as the first component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in [Ca(2+)](o) and increase action potential duration by increasing NSCC activity, thereby attenuating the impact of decreases in [Ca(2+)](o) on release probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and provide presynaptic feedback that will alter brain excitability.

Dataset Information

Alpha-Latrotoxin releases calcium in frog motor nerve terminals.

Publications

alpha-Latrotoxin releases calcium in frog motor nerve terminals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets