Induced neurotransmitter release

In squid giant axons, PbTx causes a depolarization of the plasma membrane, repetitive discharges followed by depression of action potentials, and a complete blockade of excitability. This action is antagonized by TTX (83,84). PbTx depolarizes nerve terminals and induces neurotransmitter release (85,86) it depolarizes skeletal muscle cells (87) and increases the frequency of action potentials in crayfish nerve cord (88). PbTx also produces a contraction of the guinea pig ileum (89). All these effects are prevented by TTX. 

StemauL. L., Globus M. Y., Dietrich W. D., Martinez E., Busto R., and Ginsberg M. D. (1992) Ischemia-induced neurotransmitter release effects of mild intraischemic hyperthermia. In The Role of Neurotransmitters in Brain Injury (Globus M. Y. and Dietrich W. D., eds.), Plenum Press, New York, pp. 33-38. 

There is ample precedent for a modulatory role of K channels in behavior. The K channel blocker, 4-AP, selectively blocks component T (Bartschat and Blaustein 1985a). prolongs nerve action potentials, and enhances neurotransmitter release (Llinas et al. 1975). In man, intoxication with this agent may lead to dissociative behavior, agitation, confusion, convulsions, and coma (Spyker et al. 1980). However, the behavioral aberrations induced by 4-AP differ qualitatively from those induced by PCP. This implies that block of various types of presynaptic K channels may modify behavior and mental activity however, the precise nature of the behavioral manifestations is likely to depend upon the specific type of K channel that is affected. 

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. 

Adding the second alpha-methyl to MDA gives a compound that apparently is only weakly active in man (199). Again, the 3,4-methylenedioxy substitution seems anomalous. This may also be due to an indirect effect, such as release of endogenous neurotransmitter from nerve terminals. However, neither this a,a-dimethylated MDA analog nor a,a-dimethyl-4-methoxy-/3-phenethylamine had any ability to induce the release of 3H-serotonin from rat whole brain synaptosomes (160). 

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]. 

Penile erection occurs by relaxation of the smooth muscle of the corpus cavernosum, increasing blood flow into the penis and producing erection and rigidity. In a parallel fashion, vaginal pressure stimulation increases blood velocity and flow into clitoral arteries (Lavoisier et al. 1995). Cavernosal vasodilation is accomplished by neurotransmitters released from the cavernosal nerve and endothelial cells. One of the most important transmitters in this cascade is nitric oxide (NO), which induces synthesis of cyclic GMP from guanylate cyclase (Rajfer et al. 1992). Thus, ginkgo s vascular mechanisms could be responsible for some of the putative sexual effects. 

The neurotransmitter at the sensory nerve-motor nerve synapse proved to be glutamate (incidentally, also the major excitatory neurotransmitter in the human brain). Eurther research established a basic molecular event associated with shortterm learning habituation caused the sensory neuron to release less glutamate into the synapse sensitization caused the sensory neuron to release more glutamate into the synapse. Thus, the amount of neurotransmitter released into the synapse correlates with the strength of the motor response. The release of glutamate induces an action... 

In addition to the physiological process of autoinhibition, another mechanism of presynaptic inhibition has been identified in the peripheral nervous system, although its precise relevance to the brain is unclear. In the dorsal horn of the spinal cord, for example, the axon terminal of a local neuron makes axo-axonal contact with a primary afferent excitatory input, which leads to a reduction in the neurotransmitter released. This is due to the local neuron partly depolarizing the nerve terminal, so that when the axon potential arrives, the change induced is diminished, thereby leading to a smaller quantity of transmitter being released. In the brain, it is possible that GABA can cause presynaptic inhibition in this way. 

With TMS, a brief but powerful electric current is passed through a small coil held against the scalp of a conscious patient. This generates a powerful local magnetic field which passes unimpeded through the skull and induces a weaker, less focused electric current within the brain. Due to the non-invasive nature of this method, the important physiological effects of TMS are likely to be a consequence of the density of the electric current and the electric field which is induced in the cortex. It is believed that the induced electrical fields cause neuronal depolarization which changes the neurotransmitter release mechanisms. 

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