A comparison between exocytic control mechanisms in adrenal chromaffin cells and a glutamatergic synapse

Neher, Erwin

doi:10.1007/s00424-006-0143-9

Cited by 100 publications

(96 citation statements)

References 51 publications

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“…Adrenal chromaffin cells are neuroendocrine cells in the medulla of the adrenal gland, derived from the same embryonic origin as sympathetic neurons, and are responsible for the ''fight or flight'' response of the body by releasing catecholamines epinephrine and norepinephrine into the blood stream (24). These cells are thought to share the same exocytosis mechanism as neurons, and have been widely used as a model system to study catecholamine release, including measurement of total catecholamine released per cell, quantal size (number of catecholamine molecules released per vesicle during exocytosis), and number of vesicles releasable from each cell (24,25). Amperometric recordings showed significant reductions in the total catecholamine released per cell (Ϸ50%), quantal size, and frequency of released events (Ϸ50%) in cultured chromaffin cells isolated from the KI/KI mice, when stimulated by high K ϩ (picospritzing for 6 s with an 80 mM K ϩ solution) (Fig.…”

Section: Reduced Catecholamine Release In Cultured R1441c Ki Chromaffinmentioning

confidence: 99%

R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice

Tong

Pisani

Martella

et al. 2009

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

275

267

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Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are a common genetic cause of Parkinson's disease (PD). The importance of the R1441 residue in the pathogenesis is highlighted by the identification of three distinct missense mutations. To investigate the pathogenic mechanism underlying LRRK2 dysfunction, we generated a knockin (KI) mouse in which the R1441C mutation is expressed under the control of the endogenous regulatory elements. Homozygous R1441C KI mice appear grossly normal and exhibit no dopaminergic (DA) neurodegeneration or alterations in steady-state levels of striatal dopamine up to 2 years of age. However, these KI mice show reductions in amphetamine (AMPH)-induced locomotor activity and stimulated catecholamine release in cultured chromaffin cells. The introduction of the R1441C mutation also impairs dopamine D2 receptor function, as suggested by decreased responses of KI mice in locomotor activity to the inhibitory effect of a D2 receptor agonist, quinpirole. Furthermore, the firing of nigral neurons in R1441C KI mice show reduced sensitivity to suppression induced by quinpirole, dopamine, or AMPH. Together, our data suggest that the R1441C mutation in LRRK2 impairs stimulated dopamine neurotransmission and D2 receptor function, which may represent pathogenic precursors preceding dopaminergic degeneration in PD brains.Parkinson's disease ͉ knockin ͉ dopamine D2 receptor ͉ amphetamine ͉ quinpirole

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Section: Reduced Catecholamine Release In Cultured R1441c Ki Chromaffinmentioning

confidence: 99%

R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice

Tong

Pisani

Martella

et al. 2009

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

275

267

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“…The kinetics and calcium independence of the PPR would be consistent with a mechanism as simple as binding of calcium to a single site. It is unclear whether the putative low-probability sites can be recruited at the first stimulus when calcium is raised or whether their recruitment always necessitates a conditioning pulse, as has been reported at the calyx of Held (Sakaba and Neher, 2001;Neher, 2006). If a conditioning pulse is required, the conversion of reluctant vesicles into active ones must occur rapidly but not instantaneously, thus affecting the time course of the PPR at the smaller interpulse intervals.…”

Section: Recruitment Of Release Sitesmentioning

confidence: 99%

Adaptation of Granule Cell to Purkinje Cell Synapses to High-Frequency Transmission

Valera¹,

Doussau²,

Poulain³

et al. 2012

J. Neurosci.

121

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The mossy fiber (MF)-granule cell (GC) pathway conveys multiple modalities of information to the cerebellar cortex, converging on Purkinje cells (PC), the sole output of the cerebellar cortex. Recent in vivo experiments have shown that activity in GCs varies from tonic firing at a few hertz to phasic bursts Ͼ500 Hz. However, the responses of parallel fiber (PF)-PC synapses to this wide range of input frequencies are unknown, and there is controversy regarding several frequency-related parameters of transmission at this synapse. We performed recordings of unitary synapses and combined variance-mean analysis with a carefully adapted extracellular stimulation method in young and adult rats. We show that, although the probability of release at individual sites is low at physiological calcium concentration, PF-PC synapses release one or more vesicles with a probability of 0.44 at 1.5 mM [Ca 2ϩ ] e . Paired-pulse facilitation was observed over a wide range of frequencies; it renders burst inputs particularly effective and reproducible. These properties are primarily independent of synaptic weight and age. Furthermore, we show that the PF-PC synapse is able to sustain transmission at very high frequencies for tens of stimuli, as a result of accelerated vesicle replenishment and an apparent recruitment of release site vesicles, which appears to be a central mechanism of paired-pulse facilitation at this synapse. These properties ensure that PF-PC synapses possess a dynamic range enabling the temporal code of MF inputs to be transmitted reliably to the PC.

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“…Molecules are contained in large (greater than 100 nm) electrondense vesicles [22]. Vesicle fusion requires longer-lasting depolarization than that required for release of synaptic clear vesicles [23]; in addition, calcium entry occurs through different sets of channels [24]. In response to depolarization, electrondense vesicles in chromaffin cells are transported actively towards the plasma membrane where they fuse to produce exocytosis [25].…”

Section: Problems Tackled By Papers In This Issuementioning

confidence: 99%