Abstract
The human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, sophisticated and highly efficient mechanisms are needed to enable communication among this astronomical number of elements. Such communication is made possible by synapses, the functional contacts between neurons. Two different types of synapse—electrical and chemical—can be distinguished on the basis of their mechanism of transmission. At electrical synapses, current flows through gap junctions, which are specialized membrane channels that connect two cells. In contrast, chemical synapses enable cell-to-cell communication via the secretion of neurotransmitters; these chemical agents released by the presynaptic neurons produce secondary current flow in postsynaptic neurons by activating specific receptor molecules. The total number of neurotransmitters is not known, but is well over 100. Virtually all neurotransmitters undergo a similar cycle of use: synthesis and packaging into synaptic vesicles; release from the presynaptic cell; binding to postsynaptic receptors; and, finally, rapid removal and/or degradation. The secretion of neurotransmitters is triggered by the influx of Ca2+ through voltage-gated channels, which gives rise to a transient increase in Ca2+ concentration within the presynaptic terminal. The rise in Ca2+ concentration causes synaptic vesicles to fuse with the presynaptic plasma membrane and release their contents into the space between the pre- and postsynaptic cells. Although it is not yet understood exactly how Ca2+ triggers exocytosis, specific proteins on the surface of the synaptic vesicle and elsewhere in the presynaptic terminal mediate this process. Neurotransmitters evoke postsynaptic electrical responses by binding to members of a diverse group of neurotransmitter receptors. There are two major classes of receptors: those in which the receptor molecule is also an ion channel, and those in which the receptor and ion channel are separate molecules. These receptors give rise to electrical signals by transmitter-induced opening or closing of the ion channels. Whether the postsynaptic actions of a particular neurotransmitter are excitatory or inhibitory is determined by the ionic permeability of the ion channel affected by the transmitter, and by the concentration of permeant ions inside and outside the cell.
