Classes of Neurotransmitters Much of the information transfer between neurons in the CNS occurs via chemical synapses. These synapses use a variety of messengers (neurotransmitters) that are released in a Ca2+-dependent fashion from presynaptic terminals and act on specific protein receptors to produce biochemical and excitability changes in the receiving cell. There are two primary groups of neurotransmitters—low–molecular-weight amines and neuroactive peptides. These agents act on two classes of receptors, ligand-gated ion channels, at which the binding of the transmitter directly opens ion channels in the membrane, and G protein coupled receptors. The activated G protein then acts on ion channels or alters biochemical second-messenger systems. Physiologists classify synaptic transmission according to the speed of transmission (fast or slow) and according to the nature of the response (excitatory or inhibitory).
[...] The ligand-gated ion channels gated by extracellular ATP (called P2X receptors) are exceptions to the scheme described above and have structures more typical of the inwardly rectifying channels. ATP receptors have two membrane spanning regions and a pore forming region loop) that are connected by a large loop of extracellularly located amino acids. A major difference between the P2X receptors and the inwardly rectifying channel is that the bulk of the P2X receptor is extracellular whereas the majority of the channel is intracellular. [...]
[...] The electrical principles underlying synaptic excitation or inhibition are identical to those described for voltage-gated ion channels and are based on the relative permeabilities of the ion channels and the Nernst potentials of the ions involved. Several transmitters (e.g., GABA, glutamate, acetylcholine, serotonin) act at both ligand-gated ion channels and G-protein coupled receptors. This raises the point that receptors for almost all neurotransmitters, and consequently the effects of these transmitters, are heterogeneous, with the nature of the transmitter effect depending on the specific receptor to which the transmitter binds. [...]
[...] The transmitters that act at ligand-gated ion channels increase the conductance of the cell membrane to specific ions. Excitatory transmitters, such as acetylcholine and glutamate, directly activate nonselective cationic channels, increasing the conductance to and in some cases Ca2+, while the inhibitory transmitters, GABA and glycine, increase the conductance to A second group of transmitters increases membrane conductance, but does so indirectly through a G protein. For example, GABA, serotonin, and adenosine promote G-protein–mediated opening of inwardly rectifying channels in a variety of neurons. [...]
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