|Construction of a chemical synapse|
The transmitter substances are produced in the cell body or in the terminal of the axon by the sending neuron, held in certain quantities (quantum) within synaptic vesicles and released in certain quantities (quanta) when excited. Their effect depends on the membrane equipment of the receiving cell with receptors and ion channels .
Mode of action
Neurotransmitters are messenger substances from nerve cells with which the (presynaptic) electrical signals of a neuron are converted into chemical signals at a synapse, which can again produce (postsynaptic) electrical signals in the downstream cell.
Electrical impulses, action potentials , which are transmitted into the presynaptic membrane region of the neuron , trigger the release of messenger substances from reservoirs, the synaptic vesicles , via a brief influx of calcium . This process is an exocytosis : by fusing the vesicle membranes with the presynaptic membrane, the respective quantum of transmitter molecules contained is released into the (extracellular) synaptic gap and reaches the receptors on the postsynaptic membrane of the downstream cell by diffusion .
These membrane proteins of the subsynaptic region recognize the respective transmitter specifically by its molecular spatial structure and charge distribution through complementary structures. The binding of a transmitter molecule leads to a structural change in the receptor protein, whereby directly ( ionotropic ) or indirectly ( metabotropic ) certain ion channels in this region are temporarily opened.
Depending on the number of receptors with bound transmitters, ion currents of various strengths with corresponding postsynaptic potential differences (PSP) arise. These are now - determined by the assignment of receptors in the membrane to ion channels of certain ion types - either depolarizing, so that they promote excitatory postsynaptic potential ( EPSP ) to stimulate the downstream cell or lead to the formation of an action potential, or in such a way that As an inhibitory postsynaptic potential ( IPSP ) they inhibit or prevent arousal. A distinction is made between excitatory and inhibitory synapses.
In addition to the actual neurotransmitter, it is not uncommon for cotransmitters to be released ( cotransmission ), which as neuromodulators can influence the transmission of excitation in various ways . The binding of transmitters to receptor molecules is usually reversible, so it is possible again after detachment. Their effect is limited not only by diffusion, but by enzymatic cleavage (e.g. cholinesterases ), uptake in glial cells, presynaptic re-uptake in the neuron or even postsynaptic internalization including receptor (as endocytosis ). In addition, the post-synaptic inactivation of ion channels (desensitization) is possible. Furthermore, presynaptically located autoreceptors for the transmitter can limit its release with negative feedback . In addition, numerous other presynaptic receptors are known, predominantly metabotropic G-protein-coupled receptors , which result in diverse modifications of synaptic transmission.
For the effect of a synaptic transmission, it is not the chemical substance released presynaptically as a transmitter that is decisive, but the postsynaptically developed receptivity of the downstream cell. For example, the same transmitter acetylcholine causes depolarization in skeletal muscle - mediated via ionotropic nicotinic N M choline receptors - but hyperpolarization in the heart muscle - mediated via metabotropic muscarinic M 2 choline receptors . In one case, this leads to an excitation of skeletal muscle fibers, in the other case to a decrease in the excitability of heart muscle cells.
The most important transmitter in the peripheral nervous system is acetylcholine , not only on the motor end plate of muscle fibers , but also in the parasympathetic part of the autonomic nervous system and preganglionic in the sympathetic part , postganglionic here mostly norepinephrine is released (but the sweat glands , for example, are cholinergically innervated ).
The most important neurotransmitter in the central nervous system (CNS) is glutamate , with an exciting effect; the most important transmitters of inhibitory synapses are gamma-aminobutyric acid (GABA) and glycine . Other common neurotransmitters are dopamine and serotonin in addition to acetylcholine and norepinephrine, also at synapses in the CNS.
- Derivatives of amino acids (by or after decarboxylation ) - such as dopamine or noradrenaline and adrenaline (from tyrosine , catechol-aminergic ) or histamine (from histidine , histaminergic ) or γ-aminobutyric acid (GABA) (from glutamate , GABAerge ) or serotonin (from tryptophan , serotoninergic ) - or it is
- α-amino acids - such as glycine ( glycinergic ) or glutamate ( glutamatergic ) - or they are
- Oligopeptides , i.e. short chains of composed amino acids, ( peptiderge ) - such as oxytocin , vasopressin (ADH), somatostatin (SIH), tachykinin , cholecystokinin , neurotensin and also the opioid acting neuropeptides , opioid peptides , such as endorphins .
Besides acting organophosphate of purines such as adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP) and uridine diphosphate (UDP) and uridine triphosphate (UTP) and at synapses as (co-) transmitter.
Neurotransmitters can initially be classified according to substance classes.
- Histamine (biochemical structure but different from other biogenic amines)
- Inhibitory amino acid transmitters
- Excitatory amino acid transmitters
- Ben Best: Brain Neurotransmitters (in English)
- Drugs and the Brain (in Dutch)
- Synthetic pathways of neurotransmitters (PDF file; 1.4 MB)
- Stefan Silbernagl , Agamemnon Despopoulos : Pocket Atlas Physiology . 8th edition. Thieme, Stuttgart 2012, ISBN 978-3-13-567708-8 , p. 58 and others ( limited preview in Google Book Search).
- Stefan Silbernagl, Agamemnon Despopoulos: Pocket Atlas Physiology . S. 86 f . ( limited preview in Google Book search).
- Stefan Silbernagl, Agamemnon Despopoulos: Pocket Atlas Physiology . S. 90 f . ( limited preview in Google Book search).