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One major form of communication in the NS uses neurotransmitters which are ‘squirted’ across an inter-cell channel called a ‘synapse’ or ‘synaptic cleft’. This feature is illustrated in Figure 2.3.

A wave of electrochemical excitation called an action potential travels along the membrane of the presynaptic cell, until it reaches the synapse. Channels that are permeable to calcium ions then open and calcium ions flow through the presynaptic membrane, increasing the calcium concentration in the interior. The increased calcium concentration activates a set of calcium-sensitive proteins attached to vesicles which contain a neurotransmitter. These proteins change shape, causing the membranes of some ‘docked’ vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter molecules into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells.

To use an analogy, think of a couple of crazy kids having some fun in the school cafeteria when the teacher is nowhere to be seen. In a mêlée of hundreds of children all waiting for lunch, one kid picks up a bottle of ketchup and squirts it at the other kid’s face. If the ketchup squirt hits the target, and lands squarely in the other kid’s mouth, we have a successful ‘transmission’. If he misses, he’ll have to have another go, or another kid from the crowd will need to have a squirt to achieve a successful transmission. This is the kind of thing that goes on in neurotransmission across the synapse. The first kid with the ketchup bottle is the neurone, the bottle is the synaptic vesicle, the ketchup is the neurotransmitter, the first kid’s squeezy hand is the neurotransmitter transporter, and the second kid with ketchup all over his face is the receptor. The more ketchup on the face, the better the communication. Once the ketchup has done its job, it magically returns to the bottle. Job done! Unless, of course, that tomato ketchup is the ‘wrong’ kind of neurotransmitter and the receptor kid demands a certain flavour of ice-cream instead! These ‘ketchup kid fights’ are going on trillions of times every day in each and everyone of us.

Figure 2.3 The synapse, axon terminal, dendrites and associated processes

Source: Thomas Splettstoesser, Wikimedia Commons, CC 4.0 International license

There are at least 60 different kinds of ketchup – sorry, I mean neurotransmitter – to choose from. To be a neurotransmitter, a molecule must: (1) be red, sticky and taste like ketchup [no cancel that, just checking whether you’re concentrating], be produced inside a neurone, be found in the neurone’s terminal button, and be released into the synaptic gap upon the arrival of an action potential; (2) produce an effect on the postsynaptic neurone; (3) be deactivated rapidly, after it has transmitted its signal to this neurone; (4) have the same effect on the postsynaptic neurone when applied experimentally as it does when secreted by a presynaptic neurone. The best-known neurotransmitters are:

 acetylcholine

 serotonin

 catecholamines, including epinephrine, norepinephrine and dopamine

 excitatory amino acids, such as aspartate and glutamate (half of the synapses in the CNS are glutamatergic)

 inhibitory amino acids, such as glycine and gamma-aminobutyric acid (GABA; one-quarter to one-third of the synapses in the CNS are GABAergic)

 histamine

 adenosine

 adenosine triphosphate (ATP).

Peptides form another large family of neurotransmitters, with over 50 known members, including: substance P, beta endorphin, enkephalin, somatostatin, vasopressin, prolactin, angiotensin II, oxytocin, gastrin, cholecystokinin, thyrotropin, neuropeptide Y, insulin, glucagon, calcitonin, neurotensin and bradykinin. However, many peptides act more as neuromodulators than as neurotransmitters. Neuromodulators do not propagate nerve impulses, but instead affect the synthesis, breakdown or reabsorption (reuptake) of neurotransmitters (more on this later). Curiously, certain soluble gases can also act as neurotransmitters, for example nitrogen monoxide (NO, ‘laughing gas’). These neurotransmitters have their own distinctive mechanism: they exit the transmitting neurone’s cell membrane by simple diffusion and penetrate the receiving neurone’s membrane in the same way.