Presynaptic nerve terminal

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Neurotransmitter Transporters. Figure 3 Dopamine turnover at a presynaptic nerve terminal, (a) Dopamine is produced by tyrosine hydroxylase (TH). When secretory vesicles are filled, they join the releasable pool of vesicles at the presynaptic membrane. Upon exocytosis, the diffusion of released dopamine is limited by reuptake via DAT. (b) If DAT is inactive, dopamine spreads in the cerebrospinal fluid but cannot accumulate in secretory vesicles. This results in a compensatory increase of dopamine hydroxylase activity and a higher extracellular dopamine level mice with inactive DAT are hyperactive. 

Reuptake transporters are structures within the cell membranes of the presynaptic nerve terminal that serve to transport biogenic amines released from vesicles back into the nerve cell. These structures are targets for antidepressants, which block the transporter, thus increasing the bioavailability of neurotransmitters at postsynaptic receptors. 

Bartschat, D.K. Sorensen, R.G. and Blaustein, M.P. Psychotomimetic "sigma opiates" and phencyclidines selectively block the same K channels in presynaptic nerve terminals. Soc Neurosci Abst. 11 316a, 1985. 

Galantamine is a ChE inhibitor, which elevates acetylcholine in the cerebral cortex by slowing the degradation of acetylcholine.37 It also modulates the nicotinic acetylcholine receptors to increase acetylcholine from surviving presynaptic nerve terminals. In addition, it may increase glutamate and serotonin levels. The clinical benefit of action of these additional neurotransmitters is unknown. 

Presynaptic events during synaptic transmission are rapid, dynamic and interconnected. The time between Ca2+ influx and exocytosis in the nerve terminal is very short. At the frog NMJ at room temperature, 0.5-1 ms elapses between the depolarization of the nerve terminal and the beginning of the postsynaptic response. In the squid giant synapse, recordings can be made simultaneously in the presynaptic nerve terminal and in the postsynaptic cell. Voltage-sensitive Ca2+ channels open toward the end of the action potential. The time between Ca2+ influx and the postsynaptic response as measured by the postsynaptic membrane potential is 200 ps (Fig. 10-7). However, measurements made with optical methods to record presynaptic events indicate a delay of only 60 ps between Ca2+ influx and the postsynaptic response at 38°C [21]. 

The action of catecholamines released at the synapse is modulated by diffusion and reuptake into presynaptic nerve terminals 216... 

The action of catecholamines released at the synapse is modulated by diffusion and reuptake into presynaptic nerve terminals. Catecholamines diffuse from the site of release, interact with receptors and are transported back into the nerve terminal. Some of the catecholamine molecules may be catabolized by MAO and COMT. The cate-cholamine-reuptake process was originally described by Axelrod [18]. He observed that, when radioactive norepinephrine was injected intravenously, it accumulated in tissues in direct proportion to the density of the sympathetic innervation in the tissue. The amine taken up into the tissues was protected from catabolic degradation, and studies of the subcellular distribution of catecholamines showed that they were localized to synaptic vesicles. Ablation of the sympathetic input to organs abolished the ability of vesicles to accumulate and store radioactive norepinephrine. Subsequent studies demonstrated that this Na+- and Cl -dependent uptake process is a characteristic feature of catecholamine-containing neurons in both the periphery and the brain (Table 12-2). 

Clark JM, Brooks MW (1989) Role of ion channels and intraterminal calcium homeostasis in the action of deltamethrin at presynaptic nerve terminals. Biochem Pharmacol 38 2233-2245... 

Symington SB, Frisbie RK, Lu KD, Clark JM (2007) Action of cismethrin and deltamethrin on functional attributes of isolated presynaptic nerve terminals from rat brain. Pestic Biochem Physiol 82 172-181... 

In mice carrying the mutated a2A-D79N receptor gene, presynaptic function in the vas deferens did not differ from wild-type control mice (Altman et al. 1999). This finding indicates (1) that channel coupling is not required for presynaptic function of a2A-receptors in sympathetic nerves and (2) that there is a high number of spare receptors at the presynaptic site, as expression of the a2A-D79N receptor was found to be reduced to 20% of the wUd-type level (MacMillan et al. 1996). Thus, Ca channels in presynaptic nerve terminals are essential for neurotransmitter release, and current... 

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