Calcium neurotransmitter release

Stimulation of the neuron lea ding to electrical activation of the nerve terminal in a physiologically relevant manner should eUcit a calcium-dependent release of the neurotransmitter. Although release is dependent on extracellular calcium, intracellular calcium homeostasis may also modulate the process. Neurotransmitter release that is independent of extracellular calcium is usually artifactual, or in some cases may represent release from a non-neuronal sources such as gha (3). 

Augustine GJ (2001) How does calcium trigger neurotransmitter release Curr Opin Neurobiol 11 320-326... 

The opiate receptors in the spinal cord are predominantly of the mu and delta type and are found in the C-fibre terminal zone (the substantia gelatinosa) in the superficial dorsal horn. Considerable numbers of ORL-1 receptors are also found in this area. Up to 75% of the opiate receptors are found presynaptically on the C-fibre terminals and when activated inhibit neurotransmitter release. The opening of potassium channels will reduce calcium flux in the terminal and so there will be a resultant decrease in... 

Ca2+ is necessary for transmission at the neuromuscular junction and other synapses and plays a special role in exocytosis. In most cases in the CNS and PNS, chemical transmission does not occur unless Ca2+ is present in the extracellular fluid. Katz and Miledi [16] elegantly demonstrated the critical role of Ca2+ in neurotransmitter release. The frog NMJ was perfused with salt solution containing Mg2+ but deficient in Ca2+. A twin-barrel micropipet, with each barrel filled with 1.0mmol/l of either CaCl2 or NaCl, was placed immediately adjacent to the terminal. The sodium barrel was used to depolarize the nerve terminal electrically and the calcium barrel to apply Ca2+ ionotophoretically. Depolarization without Ca2+ failed to elicit an EPP (Fig. 10-6A). If Ca2+ was applied just before the depolarization, EPPs were evoked (Fig. 10-6B). In contrast, EPPs could not be elicited if the Ca2+ pulse immediately followed the depolarization (Fig. 10-6C). EPPs occurred when a Ca2+ pulse as short as 1 ms preceded the start of the depolarizing pulse by as little as 50-100 (xs. The experiments demonstrated that Ca2+ must be present when a nerve terminal is depolarized in order for neurotransmitter to be released. 

There are at least five different types of voltage-dependent Ca2+ channel molecules, differing in their gating kinetics, modes of Ca2+-inactivation and Ca2+-iregulation, and sensitivity to specific marine toxins [13] (see Ch. 6). The distinctions between the types of channel are of considerable interest because the different subtypes are believed to subserve different cellular functions. For example, the control of neurotransmitter release in peripheral sympathetic neurons appears to be under the predominant control of N-type calcium channels. 

Tyrosine phosphorylation plays an important role in synaptic transmission and plasticity. Evidence for this role is that modulators of PTKs and PTPs have been shown to be intimately involved in these synaptic functions. Among the various modulators of PTKs, neuro-trophins have been extensively studied in this regard and will be our focus in the following discussion (for details of growth factors, see Ch. 27). BDNF and NT-3 have been shown to potentiate both the spontaneous miniature synaptic response and evoked synaptic transmission in Xenopus nerve-muscle cocultures. Neurotrophins have also been reported to augment excitatory synaptic transmission in central synapses. These effects of neurotrophins in the neuromuscular and central synapses are dependent on tyrosine kinase activities since they are inhibited by a tyrosine kinase inhibitor, K-252a. Many effects of neurotrophins on synaptic functions have been attributed to the enhancement of neurotransmitter release BDNF-induced increase in neurotransmitter release is a result of induced elevation in presynaptic cytosolic calcium. Accordingly, a presynaptic calcium-depen-dent phenomenon - paired pulse facilitation - is impaired in mice deficient in BDNF. 

The exact mechanisms by which BDNF enhances the induction of LTP remain obscure. Nevertheless, both pre-and postsynaptic mechanisms appear to be possible. As mentioned above, BDNF elevates presynaptic cytosolic calcium level and thus increases vesicular neurotransmitter release. When a postsynaptic neuron is injected with a Trk tyrosine kinase inhibitor (K252a), BDNF-augmented LTP is curtailed this suggests that a postsynaptic mechanism is adopted by BDNF in the manifestation of LTP. It has been postulated that neurotrophins may act as... 

Other target sites for certain pyrethroids include the voltage-gated calcium and chloride channels. Of particular interest is the increased effect of Type II pyrethroids on certain phosphoforms of the N-type Cav2.2 calcium channel following post-translational modification and its relationship to enhanced neurotransmitter release seen in vivo. 

Keywords CS-syndrome Neurotransmitter release Pyrethroids T-syndrome Voltage-gated calcium channels Voltage-gated sodium channels... 

Neurotransmitter release induced by potassium-dependent depolarization is a physiologically relevant way to investigate pyrethroid effects on calcium-dependent neurotransmitter release since this process is independent of voltage-sensitive sodium channels [71]. Furthermore, potassium-stimulated calcium influx and subsequent neurotransmitter release by synaptosomes is blocked by a variety of voltage-sensitive calcium channel antagonists but not by TTX [4, 71, 72]. 

Catterall WA (1998) Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release. Cell Calcium 24 307-323... 

At the cellular level, chlordecone causes spontaneous neurotransmitter release (End et al. 1981) and increases in free intracellular calcium in synaptosomes (Bondy and Halsall 1988 Bondy and McKee 1990 Bondy et al. 1989 Komulainen and Bondy 1987). This appears to be due at least in part to increased permeability of the plasma membrane (Bondy and Halsall 1988 Bondy and McKee 1990 Bondy et al. 1989 Komulainen and Bondy 1987), activation of voltage-dependent calcium channels (Komulainen and Bondy 1987), and inhibition of brain mitochondrial calcium uptake (End et al. 1979, 1981). 

The sequence of events that result in neurotransmission of information from one nerve cell to another across the s)mapses begins with a wave of depolarization which passes down the axon and results in the opening of the voltage-sensitive calcium charmels in the axonal terminal. These charmels are frequently concentrated in areas which correspond to the active sites of neurotransmitter release. A large (up to 100 M) but brief rise in the calcium concentration within the nerve terminal triggers the movement of the synaptic vesicles, which contain the neurotransmitter, towards the synaptic membrane. By means of specific membrane-bound proteins (such as synaptobrevin from the neuronal membrane and synaptotagrin from the vesicular membrane) the vesicles fuse with the neuronal membrane and release their contents into the synaptic gap by a process of exocytosis. Once released of their contents, the vesicle membrane is reformed and recycled within the neuronal terminal. This process is completed once the vesicles have accumulated more neurotransmitter by means of an energy-dependent transporter on the vesicle membrane (Table 2.3). 

C. The purpose of this question is to clarify the cellular mechanism of analgesia produced by morphine. First, morphine blocks the transmission of nociceptive impulses. In that case, the relevant question is how nociceptive impulses are transmitted via the release of pronociceptive neurotransmitters. The question then is to determine which intracellular process favors a block of release of neurotransmitters. The correct answer is C because calcium is required for neurotransmitter release. Blocking potassium efflux and increasing calcium channel phosphorylation produce functional depolarization and neurotransmitter release. Opioids are coupled to Gj (inhibitory proteins) that decrease cAMP. 

Calcium play vital role in excitation - contraction coupling in myocardium. Calcium mediates contraction in vascular and other smooth muscles. Calcium is required for exocytosis and also involved in neurotransmitters release. Calcium also help in maintaining integrity of mucosal membranes and mediating cell adhesions. Hypercalcemia may occur in hyperthyroidism, vitamin D intoxication and renal insufficiency, which can be treated by administration of calcitonin, edetate sodium, oral phosphate etc. Hypocalcemia may occur in hypothyroidism, malabsorption, osteomalacia secondary to leak of vitamin D or vitamin D resistance, pancreatitis and renal failure. Hypocalcemia can be treated by chloride, gluconate, gluceptate, lactate and carbonate salts of calcium. 

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