Nervous system intercellular communication

CX3CL1 as Mediators of Intercellular Communication in the Nervous System... 

Gap junctions provide in the nervous system the structural correlate of one class of electrical synapses, characterized by very close apposition between the presynaptic and postsynaptic membranes. It should be noted, in this respect, that different junctional specializations can mediate different forms of electrical transmission between neurons (Bennett, 1997). Electrical synapses transmit preferentially, but not exclusively, low-frequency stimuli, that allow the rapid transfer of a presynaptic impulse into an electrical excitatory potential in the postjunctional cells. Electrical transmission, via the intercellular channels, can be bidirectional. The widely held opinion that electrical transmission is characteristic of lower vertebrates probably derives from the large cell systems in which electrical synapses were identified in the initial period of intracellular recording (reviewed by Bennett, 1997). Contradicting this view, electrotonic coupling between neurons has now been demonstrated in many areas of the mammalian central nervous system and has been implicated in neuronal synchronization. Gap junctional intercellular communication can occur between glial cells, glia and neurons, as well as between neurons. 

Phosphorylation. Phosphorylation is a posttranslational modification that is reflected in close to 30% of eukaryotic gene products and almost 2% of the human genome-encoded protein kinases. Protein phosphorylation plays an essential role in intercellular communication during development, in physiological responses and homeostasis, and in the functioning of the nervous and immune systems. Reversible phosphorylation regulates many diverse... 

Specific receptors on the plasma membrane of a target cell are an important component for mediating intercellular communication (83), but this is not the only mechanism by which a message is carried into the cell. In the central nervous system, for example, a presynaptic neuron may release neuromodulating molecules but the postsynaptic cell lacks definable receptors for that molecule. But taken up into the postsynaptic cell by a high-afBnity transport mechanism (80), the neuromodulator can alter the response to a neurotransmitter for which a receptor mechanism clearly exists. Presumably the former has altered the receptor or a postreceptor mechanism for the latter. 

Intercellular communication in the nervous system is typically mediated through synaptic transmission via the release of neurotransmitters and their subsequent binding to specific receptors. The transmitter-receptor interaction then elicits changes in ion channel permeability and/or second messenger formation in the innervated cell. Neurotransmitters can also interact with receptors located on the presynaptic terminal (either autoreceptors, which are activated by the same transmitter, or heteroreceptors, which are activated by a different transmitter released by a different neuron) to regulate the presynaptic function, often by influencing neurotransmitter release. Termination of synaptic neurotransmission depends upon the removal of neurotransmitter molecules from the synaptic cleft by either enzymatic degradation or by reuptake into the presynaptic terminal. 

The nervous system is complex both anatomically and functionally. The extensive networks mediating intracellular and intercellular communications make it highly vulnerable to disruption by many toxicants. Moreover, the nervous system possesses additional unique features that can contribute to its higher sensitivity to toxicants, including CWAs. 

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