ABSTRACT
Communication among unconnected cells requires the release of extracellular messengers and specific receptor mechanisms on, or in, the target cells. Signalling substances include hormones, neurotransmitter substances, trophic factors and diffusible substances. In higher organisms, synaptic transmission is the principal method of communication between cells, especially in the nervous system. Nerve cells mediate fast signalling between sensory systems and the central nervous system (CNS) and between the CNS and effector systems. Within the CNS, nerve cells form complex circuits that serve the integration of inputs and the generation of specific activity patterns. Synaptic transmission is the most important means by which nerve cells communicate. There are two principal types of synaptic transmission; electrical and chemical. Electrical transmission involves ion fluxes across membranes. In many cases, synaptic transmission is chemical and involves the secretion of signalling substances. In most cases, the termination of chemical transmission is achieved by rapid uptake of the released neurotransmitter by specific high-affinity neurotransmitter transporters into the synaptic terminal or the surrounding glial cells (Kuhar, 1973; Iversen and Kelly, 1975; Kanner, 1983, 1989; Kanner and Schuldiner, 1987). It has been known for many years that neurones and glia can accumulate neurotransmitters by Na+-dependent transport processes. Neurotransmitters are cotransported with Na+ utilizing the energy stored in transmembrane electrochemical gradients generated by primary ion pumps (Kanner, 1983). Studies on neurotransmitter uptake have demonstrated the existence of multiple uptake systems, each relatively selective for a specific neurotransmitter. Neurotransmitters are transported across membranes by at least four distinct families of transporters: (1) vesicular transporters that function in the uptake of neurotransmitters into synaptic vesicles and granules (Schuldiner, 1994); (2) Na+- and Cl−-dependent (Na+/Cl−) transporters that operate on the plasma membrane of neuronal and glia cells (Uhl, 1992; Schloss et al. 1992; Amara and Kuhar, 1993); (3) Na+/K+-dependent transporters that function on the plasma membranes, especially in glutamate transport (Kanner, 1993); and (4) general amino acid transport systems that participate in controlling the availability of neurotransmitters outside the cells (McGivan and Pastor-Anglada, 1994).
