Vesicular release

Precise kinetic electroanalytical data permit to describe quantitatively the kinetics of the whole process with a precision that has never been achieved before by patch-clamp techniques or spectroscopic near-field methods. This enables to investigate finely these events and to identify the exact physicochemical nature of all the individual physicochemical and biological factors which concur to produce vesicular release. 

Adenosine production in the synapse is not through vesicular release in response to nerve firing, as is the case for classical neurotransmitters. Rather, adenosine acts as a local autacoid, the release of which increases upon stress to an organ or tissue. Most cells in culture and in situ produce and release adenosine extracellularly. This... 

Fig. 1.—Diagrammatic Representation of the Three Steps in the Taste-cell Transduction. Step 1, interaction of stimulus (S) with membrane-bound receptor (R) to form stimulus-receptor complex (SR) step 2, conformational change (SR) to (SR), brought about by interaction of S with R (this change initiates a change in plasma-membrane conformation of taste cells, probably below the level of the tight junction) and step 3, conformational changes of the membrane result in lowered membrane resistance, and the consequential influx on intracellular ionic species, probably Na. This influx generates the receptor potential which induces synaptic vesicular release to the innervating, sensory nerve, leading to the generator potential.

ACh and considered to be the vesicles in the labile releasable pool. The evidence for and the actual mechanism of the vesicular release of ACh, mostly gained from studies at peripheral synapses, has been covered in Chapter 4. 

By maintaining low concentrations of cytoplasmic noradrenaline, MAO will also regulate the vesicular (releasable) pool of transmitter. When this enzyme is inhibited, the amount of noradrenaline held in the vesicles is greatly increased and there is an increase in transmitter release. It is this action which is thought to underlie the therapeutic effects of an important group of antidepressant drugs, the MAO inhibitors (MAOIs) which are discussed in Chapter 20. 

Increase release. This should follow block of any presynaptic inhibitory autoreceptors. It is not practical at present to increase the vesicular release of a particular NT. 

The chemical synapse is a highly specialized structure that has evolved for exquisitely controlled voltage-dependent secretions. The chemical messengers, stored in vesicles, are released from the presynaptic cell following the arrival of an action potential that triggers the vesicular release into the presynaptic terminal. Once released from the vesicles, the transmitter diffuses across a narrow synaptic cleft, then binds to specific receptors in the postsynaptic cell, and finally initiates an action potential event in the nerve-muscle cell membrane by triggering muscle contractions. 

Matsui K. and Jahr C. E. (2004). Differential control of synaptic and ectopic vesicular release of glutamate. J. Neurosci. 24 8932-8939. 

Aristotle (350 B.C.) History of Animals. In Barnes J (ed) The complete works of Aristotle The revised Oxford translation, 1984, Princeton, Princeton University Press Ashton AC, Rahman MA, Volynski KE et al (2000) Tetramerisation of a-latrotoxin by divalent cations is responsible for toxin-induced non-vesicular release and contributes to the Ca2+-dependent vesicular exocytosis from synaptosomes. Biochimie 82 453-68 Ashton AC, Volynski KE, Lelianova VG et al (2001) a-Latrotoxin, acting via two Ca2+-dependent pathways, triggers exocytosis of two pools of synaptic vesicles. J Biol Chem 276 44695-703 Auger C, Marty A (1997) Heterogeneity of functional synaptic parameters among single release sites. Neuron 19 139-50... 

Verhaeghe RH, Vanhoutte PM, Shepherd JT (1977) Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides. Circ Res. 1977 40 208-15 Volknandt W (2002) Vesicular release mechanisms in astrocytic signalling. Neurochem Int 41 301-6... 

Basically, then, NO seems to be able to modulate vesicular release of transmitter in either direction, or not at all, depending on the coincident level of presynaptic activity and NO concentration. The concept of an activity-dependent retrograde NO signal that is generated in the postsynapse and then diffuses into the presynapse to regulate transmitter release has been investigated extensively, due to its possible involvement in neuronal excitability and memory processes (see Section 3.2.1). 

Szatkowski, M., Barbour, B., and Attwell, D. (1990). Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Nature 348, 443—446. 

Raiteri, L., Raiteri, M., and Bonanno, G. (2001). Glycine is taken up through GLYT1 and GLYT2 transporters into mouse spinal cord axon terminals and causes vesicular release of its proposed cotransmitter GABA. J. Neurochem. 76, 1823—1832. 

Verkhratsky, A., and Steinhauser, C. (2000). Ion channels in glial cells. Brain Res. Rev. 32, 380-412. Volknandt, W. (2002). Vesicular release mechanisms in astrocytic signalling. Neurochem. Int. 41,... 

BoNTs are a group of immunologically distinct but closely related bacterial proteins that act as potent inhibitors of synaptic transmission in skeletal muscle. Inhibition of ACh release from the presynaptic terminal of the neuromuscular junction (NMJ) is thought to be the sole mechanism involved in the toxins lethal action (Sellin, 1985 Simpson, 1986) and therefore the cause of botulism. The pathogenesis of intoxication is not completely understood but is generally thought to involve a multistep process to interrupt normal vesicular release of ACh Ifom the presynaptic motor nerve... 

In general, the process of vesicular release can be summarized as follows During or after the biosynthesis of the neurotransmitter, the substance is packaged into synaptic vesicles at the nerve terminals. Here the transmitter is stored until the nerve terminal is depolarized by the appearance of an action potential, at which time Ca " enters the cell and permits the exocytotic process that involves the apparent fusion of vesicular membranes with the plasmalemma. Such fusion allows for the release of the transmitter that is packaged within the vesicle. Regulatory mechanisms that are not presently clear then lead to the recycling of the vesicle within the nerve ending. In-depth reviews of release processes can be found in Cooke et al. (1973), Krnjevic (1974), Katz (1969), Rubin (1970), Zimmerman (1979), and Kelly et al. (1979). 

The release of ACh and other neurotransmitters by exocytosis is inhibited by botulinum and tetanus toxins from Clostridium. Botulinum toxin acts in the nerve ending to reduce ACh vesicular release (see Chapters 9 and 63 for therapeutic uses of botulinum toxin). 

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