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Starting with the synapse at rest, synaptic vesicles loaded with neurotransmitter (·, Tr) are concentrated in the axon terminal, and an action potential travels down the nerve fiber to the axon terminal. Upon depolarization of the axon terminal, calcium enters and triggers fusion of synaptic vesicles with the synaptic membrane of the pre-synaptic cell, a process that involves specific interactions between a number of proteins. At this point, the contents of the synaptic vesicles (i.e., neurotransmitters) are released into the synaptic cleft (1) where they diffuse to the post-synaptic cell membrane, bind specifically to a receptor (2) and open a channel for sodium (with depolarization of the post-synaptic cell) or chloride (with hyperpolarization of the post-synaptic cell). In order to terminate the signal, the neurotransmitter is transported back into the pre-synaptic cells via neurotransmitter re-uptake proteins that are specific for different neurotransmitters (3). Transport is usually sodium-coupled, but frequently, translocation of other ions (K+ or Cl-) is also required for accumulation. Once inside of the axon terminal, the neurotransmitters are actively transported and re-packaged in synaptic vesicles (4). There is a so-called vacuolar ATPase on the outer surface of the synaptic vesicle membrane that utilizes ATP hydrolysis to pump protons into the synaptic vesicles, thereby generating a ∆µH+ (interior positive and acid, as in ISO E. coli membrane vesicles). The neurotransmitter is then actively transported into the synaptic vesicles by means of specific antiporters in the synaptic vesicle membrane (i.e., protons move out of the synaptic vesicles down their electrochemical gradient, and the energy released by this process is used to accumulate neurotransmitter against a concentration gradient). The synaptic vesicles in the pre-synaptic axon terminal are now reloaded and ready to release neurotransmitter again.