Cellular Neuroscience - Neurotransmitter Transporters, Receptors, and Signaling Mechanisms

Neurotransmitter Transporters, Receptors, and Signaling Mechanisms

After neurotransmitters are synthesized, they are packaged and stored in vesicles. These vesicles are pooled together in terminal boutons of the presynaptic neuron. When there is a change in voltage in the terminal bouton, voltage-gated calcium channels embedded in the membranes of these boutons become activated. These allow Ca2+ ions to diffuse through these channels and bind with synaptic vesicles within the terminal boutons. Once bounded with Ca2+, the vesicles dock and fuse with the presynaptic membrane, and release neurotransmitters into the synaptic cleft by a process known as exocytosis. The neurotransmitters then diffuse across the synaptic cleft and bind to postsynaptic receptors embedded on the postsynaptic membrane of another neuron. There are two families of receptors: ionotropic and metabotropic receptors. Ionotropic receptors are a combination of a receptor and an ion channel. When ionotropic receptors are activated, certain ion species such as Na+ to enter the postsynaptic neuron, which depolarizes the postsynaptic membrane. If more of the same type of postsynaptic receptors are activated, then more Na+ will enter the postsynaptic membrane and depolarize cell. Metabotropic receptors on the other hand activate second messenger cascade systems that result in the opening of ion channel located some place else on the same postsynaptic membrane. Although slower than ionotropic receptors that function as on-and-off switches, metabotropic receptors have the advantage of changing the cell's responsiveness to ions and other metabolites, examples being Gamma Amino-Butyric Acid (inhibitory transmitter), Glutamic Acid (excitatory transmitter), Dopamine, Norepinephrine, Epinephrine, Melanin, Serotonin, Melatonin, and Substance P.

Postsynaptic depolarizations can be either excitatory or inhibitory. Those that are excitatory are referred to as excitatory postsynaptic potential (EPSP). Alternatively, some postsynaptic receptors allow Cl- ions to enter the cell or K+ ions to leave the cell, which results in an inhibitory postsynaptic potential (IPSP). If the EPSP is dominant, the threshold of excitation in the postynaptic neuron may be reached, resulting in the generation and propagation of an action potential in the postynaptic neuron.