Neurotransmitter release at rapid synapses
Introduction
The release of peptides, monoamines or rapid neurotransmitters displays a variety of different kinetics and Ca2+-dependencies even when tested on the same cell, suggesting differences in the underlying molecular mechanisms [1], [2]. In the ‘kiss-and-run’ process the vesicles recycle without undergoing full fusion with the plasma membrane, release occurring through a fusion pore [3], [4]. In another case, the core of the granules is transiently exposed at the external surface of the secreting cell but is re-internalised by endocytosis a few minutes after the secretion stimulation [5]. Also channels located in vesicle membrane and/or at the plasmalemma were proposed to modulate secretion and to bring appropriate charges for exchange with secretion products bound in the granule matrix [6]. Channels have also been proposed at the plasma membrane to establish fusion pores, connecting the vesicle lumen with the extracellular space [7]. In the present review, it will be shown that transmitter-specific channels may ensure the formation of neurotransmitter quanta [8]. Such a diversity will probably help to solve many discrepancies encountered in the past among the data obtained using different approaches and different preparations. Our aim here is to gather ancient and recent observations concerning the release of acetylcholine (ACh) in rapid synapses, which are defined as synapses operating in the millisecond range and where, in addition to a vesicular compartment, the cytosolic concentration of neurotransmitter is relatively high (mM range).
Section snippets
Variations of cytoplasmic ACh explain the release kinetics during repetitive nerve stimulation
In their classical work, Birks and MacIntosh [9] investigated the metabolism of ACh in sympathetic ganglia before and after nerve stimulation. They found that at the onset of activity the synapses utilise an immediately available pool of transmitter. After some delay, ACh resynthesis occurs, compensating for utilisation and maintaining from that time on the output at a steady state level for a long period, provided that the perfusion contains the necessary metabolic substrates. In these
Conclusions
About half of ACh of the nerve terminals is present in the cytoplasm, which is also the compartment where synthesis takes place. Cytoplasmic ACh is consumed and rapidly renewed on stimulation with kinetics which are typically reflected in the efficiency of synaptic transmission. Mediatophore, to our knowledge, is the only protein which is able to release ACh in Ca2+-dependent and quantal manner, which are the most characteristic features of natural synapses. It will be fascinating in a near
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2012, Neurochemistry InternationalCitation Excerpt :To assess the validity of this mechanism, we used mediatophore, a 16-kDa proteolipid originally found in the presynaptic membrane of the Torpedo electric organ (Israël et al., 1986, 1991). Mediatophore was later shown to be an ortholog of mammalian C subunit in the V0 transmembrane sector of vacuolar proton ATPase (ATP6V0C; Nezu et al., 1992; Dunant and Israël, 2000; Hinton et al., 2009; Ediger et al., 2009; Di Giovanni et al., 2010; El Far and Seagar, 2011). ATP6V0C forms a proteinaceous pore (Zimmerberg, 2001; Dunant and Israël, 2000; Morel et al., 2001; Drory et al., 2004; Inoue and Forgac, 2005; Drory and Nelson, 2006; Zhang et al., 2006) and mediates the Ca2+-dependent and fast release of acetylcholine (ACh; Falk-Vairant et al., 1996a,b; Dunant and Israël, 2000; Malo and Israël, 2003; Dunant et al., 2009).
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