Neurotransmitters

Neurotransmitters

        The transmission of impulses through synapses involves the release of chemical substances called neurotransmitters that are present within synaptic vesicles. When a nerve impulse reaches a terminalbouton neurotransmitter is released into the synaptic cleft. Under the influence of the neurotransmitter the postsynaptic surface becomes depolarised resulting in a nerve impulse in the postsynaptic neuron. In the case of inhibitory synapses, the presence of the neurotransmitter causes hyperpolarisation of the postsynaptic membrane. The neurotransmitter released into the synaptic cleft acts only for a very short duration. It is either destroyed (by enzymes) or is withdrawn into the terminal bouton.

        When an action potential reaches the presynaptic terminal, voltage sensitive calcium channels are opened up so that there is an influx of calcium ions leading to a series of chemical changes. As a result of these changes synaptic vesicles pour the neurotransmitter stored in them into the synaptic cleft. The neurotransmitter reaches and binds onto receptor molecules present in the postsynaptic membrane. This alters permeability of the postsynaptic membrane to ions of calcium, sodium, potassium or chloride leading to depolarisation (or hyperpolarisation at inhibitory synapses). The best known (or classical) neurotransmitters responsible for fast but short-lived action of the kind described above are acetylcholine, noradrenaline and adrenaline. For long, all nerve terminals were regarded as either cholinergic or adrenergic, until it was recognised that these were not the only neurotransmitters present. Other fast neurotransmitters whose presence is now well established are dopamine and histamine.

        It is also recognised that apart from the neurotransmitters mentioned above numerous other chemical substances are associated with synapses. Some of these, which probably act as neuro-transmitters, are serotonin, gama-aminobutyric acid (GABA), glutamate, aspartate and glycine.

        It is now known that at some synapses the effect of a neurotransmitter may last for seconds or even minutes. Repeated synaptic activity can have long lasting effects on the receptor neuron including structural changes such as the formation of new synapses, alterations in the dendritic tree, or growth of axons. Such effects produced under the influence of chemical substances are described as neuromediation, the chemical substances concerned being called neuromediators. This term includes neurohormones, synthesised in neurons and poured into the blood stream through terminals resembling synapses in structure. Similar chemical substances are also poured into the cerebrospinal fluid or into intercellular spaces to influence other neurons in a diffuse manner.

        Lastly, some chemical substances associated with synapses do not influence synaptic transmission directly, but influence the effects of transmitters or of neuromediators. Such chemical substances are referred to as neuromodulators. Several peptides found in the nervous system probably act as neuromodulators. These include substance P, vasoactive intestinal polypeptide (VIP), somatostatin, cholecystokinin and many others.

        The following factors can influence synaptic transmission (and thereby the speed of responses).

a.              Drugs like caffeine produce their stimulatory effect by stimulating synaptic transmission.

b.              Synaptic transmission may decrease in old age because calcium ion channels become fewer. In the case of the heart this may impair the stimulating effect of exercise on heart rate and cardiac output.

c.               Synaptic transmission is disturbed in some diseases like myasthenia gravis.

d.               It is also affected in poisoning by organophosphates. In this condition the action of acetylcholine esterase is inhibited and acetyl choline accumulates. This can lead to spasm of respiratory muscles and death.