Neuron transmission

Laduron, PM (1985) Presynaptic heteroceptors in regulation of neuronal transmission. Biochem. Pharmacol. 34 467 70. 

Many brain and spinal cord neurons have the capacity to produce NO and experimental evidence indicates a role for this gas in neuronal transmission in animals. A major issue is that the effects of a gas are not limited to the release site and interpretation of the apparent neuronal actions of NO is complicated by the fact that some of the observed effects may be via changes in local blood flow. 

The function of a neuron is to communicate or relay information to another cell by way of an electrical impulse. A synapse is the site at which the impulse is transmitted from one cell to the next. A neuron may terminate on a muscle cell, glandular cell, or another neuron. The discussion in this chapter will focus on neuron-to-neuron transmission. At these types of synapses, the presynaptic neuron transmits the impulse toward the synapse and the postsyn-aptic neuron transmits the impulse away from the synapse. Specifically, it is the axon terminal of the presynaptic neuron that comes into contact with the cell body or the dendrites of the postsynaptic neuron. Most neurons, particularly in the CNS, receive thousands of inputs. As will become evident, the transmission of the impulse at the synapse is unidirectional and the presynaptic neuron influences activity of the postsynaptic neuron only. 

In this chapter, we provide a brief overview of voltage-gated calcium channel subtypes and function, with an emphasis on neuronal transmission. The structure and kinetics of calcium channels is an extensive field of study, and outstanding reviews have recently appeared [3,4]. This chapter is focused on the potential opportunities for small-molecule intervention in neuronal signaling via antagonism of voltage-gated calcium channel subtypes, with a brief review of the chemotypes that have been recently reported to modify channel function. 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

As agents blocking conductivity in axons and dendrites, local anesthetics differ from the compounds that block neuron transmission in synapses. 

Activation of K+ channels, inactivation of Ca2+ channels and direct inhibition of neurotransmitter release are powerful mechanisms by which opioids inhibit the neuronal transmission of the pain signal. 

Sparteine is a drug with antiarrhythmic properties. It has been deduced from pharmacological and electrophysiological studies that sparteine acts via a reduction of the Na inward current, e.g. during the upstroke of cardiac action potentials. This process was elucidated by the determination of sodium currents, in isolated muscle fibbers, by loose patch clamp measurements [236]. The IC50 value for half-maximal blocking of the sodium current was 168.8 )iM, which is in accordance witli the antiarrhythmic activity of sparteine. The importance of sparteine on Na channels inhibition was further analysed because of its potencial strong interference in neuronal transmission, particularly in herbivores. This emphasizes the role of sparteine as a chemical defence compound for the plants that produce it. 

Diazepam, the most commonly used benzodiazepine in equine medicine, is used as a component of anesthetic protocols (see Ch. 15) and for the treatment of seizures (see Ch. 9). It induces skeletal muscle relaxation by facilitating the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) within the central nervous system. It acts primarily within the spinal cord and exerts inhibitory effects on polysynaptic reflexes and intemuncial neuron transmission. 

The active moieties of marijuana have been studied for medicinal purposes in a variety of models. Some canabinoids have displayed effects on neuronal transmission and alterations of calcium homeostasis. Other cannabinoids have been shown to stimulate cell death (apoptosis), which may help explain observed antitumor effects in some animal models. 

Neurochemical investigations performed in transporter mutant mice clearly illustrate that elimination of the active transport process results in a fundamental shift in the mode of neuronal transmission (23-25, 36, 39, 89) (Table 1). Absence... 

The neuronal monoamme transporters provide the principal mechanism for rapid termmation of the signal in neuronal transmission, whereas the transporters at extraneuronal locations are more important for limiting the spread of the signal and for clearance of catecholamines from the bloodstream. For the norepinephrine released by sympathetic nerves, about 90% is removed back into nerves by neuronal uptake, 5% is removed by extraneuronal uptake, and 5% escapes these processes to enter the bloodstream. In contrast, for the epinephrine released directly into the bloodstream from the adrenals, about 90% is removed by extraneuronal monoamine transport processes that are particularly important in the liver. The presence of these highly active transport processes means that monoamines are rapidly cleared from the bloodstream with a circulatory half-life of less than 2 minutes. 

As the spine s vibratory frequency is quickened, neuron transmissions reach peak output and brain activity is heightened. The senses are also heightened, pushing thought through new neural pathways, opening up unexplored avenues of perception... 

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