Vesicle release machinery

The activity of N-type and P/Q-type calcium channels is also regulated by proteins that form part of the synaptic vesicle release machinery (Figure 3). These channel subtypes contain a specific synaptic protein interaction site (termed synprint) in the... 

Jarvis SE, Zamponi GW (2005) Masters or slaves Vesicle release machinery and the regulation of presynaptic calcium channels. Cell Calcium 37 483-8 Jun K, Piedras-Renteria ES, Smith SM, Wheeler DB, Lee SB, Lee TG, Chin H, Adams ME, Scheller RH, Tsien RW, Shin HS (1999) Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(l A)-subunit. Proc Natl Acad Sci U S A 96 15245-50... 

Fig. 3 Mechanisms involved in the opioid ( r, 8, k, ORLi) and neuropeptide Y (Y2) receptor-mediated inhibition of exocytotic transmitter release. Following activation of the respective receptor and Gi/0 (1), three signal transduction pathways are possible, namely inhibition of voltage-dependent Ca2+ channels (2), opening of K+ channels (3), and a direct inhibitory effect on the vesicle release machinery (4). Glossary — > - leading to => - ion flux => - action potential Vm - membrane potential (+) and mean stimulatory and inhibitory effect, respectively.

Y receptors in the rat spinal cord a direct effect on the vesicle release machinery (step 4 in Figure 3) can be assumed, since agonists inhibited the frequency of the miniature inhibitory or excitatory postsynaptic currents (Moran et al. 2004 italics in Table 3). 

Since the orexin receptors are Gq protein-coupled (Alexander et al. 2006), one may assume that this also holds true for the presynaptic orexin receptor(s), but so far no data are available. Nonetheless, the six studies carried out in central nervous preparations permit some conclusions on the post-G protein mechanisms. In all instances, the orexins increased the frequency of spontaneous inhibitory or excitatory postsynaptic potentials or currents. The results differed, however, with respect to the influence of tetrodotoxin. In the medial and lateral hypothalamus (van den Pol et al. 1998 Li et al. 2002), dorsal vagal complex (Davis et al. 2003), and caudal nucleus tractus solitarii (Smith et al. 2002), orexins increased the frequency of the miniature potentials or currents also in the presence of tetrodotoxin, suggesting that they directly influenced the vesicle release machinery (references in italics in Table 5). On the other hand, in the prefrontal cortex (Lambe and Aghajanian 2003) and lat-erodorsal tegmentum (Burlet et al. 2002), the orexins did not retain their facilitatory effect in the presence of tetrodotoxin, suggesting an effect further upstream e.g., on Ca2+ and/or K+ channels. 

Glutamate Rat Cortex (brain slice) Electrophysiology (patch clamp) Vesicle release machinery inhibited Auclair etal. 2000... 

AP evoked release) Vesicle release machinery not inhibited ... 

In conclusion, there are examples for presynaptic inhibition by all three mechanisms inhibition of voltage-dependent calcium channels, activation of potassium channels and inhibition of the vesicle-release machinery. The inhibitory mechanisms vary in different types of axon terminals. One axon terminal can possess several inhibitory mechanisms (for example, calcium channels and vesicle release can be inhibited simultaneously). 

Fig. 8. Effects of cannabinoids on synaptic transmission. Activation ofthe CBq receptor at the presynaptic axon terminal inhibits transmitter release from the synaptic vesicle. Three mechanisms can be involved in presynaptic inhibition X refers to unknown second messengers) inhibition of voltage-dependent calcium channels, activation of potassium channels and direct interference with the vesicle release machinery.TheCBi receptor can be activated by exogenous agonists, but also by the endocannahinoids anandamide (A 4) and 2-arachidonoylglycerol (2-AG i, which are released from the postsynaptic neuron by passive and/or facilitated diffusion. The synthesis of endocannahinoids is triggered by a depolarisation-induced ( / , membrane potential) calcium influx or by activation ofGq/n protein-coupled receptors...

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