synaptictransmission
- 1. Chemicals involved in synaptic transmission
- 2. content Introduction of neuron Chemically and electrically synapse structure Process of transmission chemical substance that function as transmission small and large molecules storage of acetylcholine in synaptic vesicles overview of chemical synapse
- 3. Introduction Neurons receive information from sensory organs, send information to motor organs, or share information with other neurons. The process of communicating information is very similar, whether it is to another neuron or to a muscle or gland cell. However, by far the largest number of neuronal connections is with other neurons. The rest of this tutorial therefore focuses on inter- neuronal communication. The transmission of information is accomplished in two ways: Electrically Chemically
- 4. Electrically: the neuron is directly adjacent to other neurons. Small holes in each cell's membrane, called gap junctionsare juxtaposed so that as the action potential reaches the end of the axon Chemically: there is a space (the synaptic cleft) between the axon terminus and the adjacent neuron. As the action potential reaches the end of the axon, a chemical is released that travels across the synaptic cleft to the next neuron to alter its electric potential
- 5. Synapse Structure The part of the synapse that belongs to the initiating neuron is called the presynaptic membrane. The part of the synapse that belongs to the receiving neuron is called the postsynaptic membrane. The space between the two is called the synaptic cleft. It is approximately 20 nm wide (20 x 10-9 m).
- 6. Synapse structure Presynaptic terminals contain numerous synaptic vesicles Synaptic vesicles contain Neurotransmitters, chemical substances which ultimately cause postsynaptic changes in the receiving neuron, is contained within the synaptic vesicles. Common neurotransmitters include: Acetylcholine Dopamine Norepinepherine (a.k.a., noradrenaline) Serotonin
- 7. Transmission Chemical transmission, including the ability to excite or inhibit the postsynaptic cell. Here the conduction of information can cause either depolarization or hyperpolarization, depending on the nature of the chemical substance. The sequence of events that lead to postsynaptic changes is as follows: 1.The action potential signal arrives at the axon terminal. 2.The local depolarization causes Ca2+ channels to open.
- 8. 3.Ca2+ enters the presynaptic cell because its concentration is greater outside the cell than inside. 4.The Ca2+ , by binding with calmodulin, causes vesicles filled with neurotransmitter to migrate towards the presynaptic membrane. 5. The vesicle merges with the presynaptic membrane 6. The presynptic membrane and vesicle now forms a continuous membrane, so that the neurotransmitter is released into the synaptic cleft. This process is called exocytosis. 7. The neurotransmitter diffuses through the synaptic cleft and binds with receptor channel membranes that are located in both presynaptic and postsynaptic membranes 8. The time period from neurotransmitter release to receptor channel binding is less than a millionth of a second
- 10. The process of transmission is depicted in diagram:
- 11. Chemical substances that function as synaptic transmission More than 50 chemical substances have been proved or postulated to function as synaptic transission. Many of them are listed in which give two groups of synaptic transmitters. small molecules large molecules
- 12. Small molecules: The small-molecule, rapidly acting transmitters that cause most acute responses of the nervous system, such as transmission of sensory signals to the brain and of motor signals back to the muscles. Large molecules: The neuropeptides, in contrast, usually cause more prolonged actions, such as long-term changes in numbers of neuronal receptors, opening or closure of certain ion channels, and possibly even longterm changes in numbers of synapses or sizes of synapses.
- 13. Small-Molecule, Rapidly Acting Transmitters Class I Acetylcholine Class II: The Amines Norepinephrine Epinephrine Dopamine Serotonin Histamine Class III: Amino Acids Gamma-aminobutyric acid (GABA) Glycine Glutamate Aspartate Class IV Nitric oxide (NO)
- 14. Storage of acetylcholine (ACh) in synaptic vesicles 40 nm diameter membrane bounded vesicles Contain 1000 to 10,000 molecules of acetylcholine A single axon terminus may contain a million or more vesicles contacting the target cell at several hundred points
- 15. Acetylcholine ACh is a transmitter that is in a class by itself: It is synthesized in terminals from acetyl CoA and choline by choline acetyltransferase. It is packaged in vesicles in the axon terminals. It can bind to two distinct receptor types: nicotinic and muscarinic. Nicotinic receptors are seen in the skeletal muscle synapse and at synapses within the CNS. Muscarinic receptors for ACh are also seen in the CNS and at parasympathetic synapses on target tissues. After release, ACh is degraded by the enzyme acetylcholinesterase into acetate and choline. The choline is taken back into the terminal by Na+ - driven facilitated uptake.
- 17. Synthesis of acetylcholineTakes place in cytosol of axon terminals
- 18. Characteristics of Some of the More Important Small-Molecule Transmitters. Small Molecules Acetylcholine (ACh) Uses choline as a precursor Choline cannot be synthesized by the body and must be obtained from external food sources Used by motor neurons as an excitatory neurotransmitter in the spinal cord
- 19. Acetyl choline Used by the Autonomic Nervous System, such as smooth muscles of the heart, as an inhibitory neurotransmitter in preganglionic neurons and postganglionic parasympathetic neurons. Used everywhere in the brain. For example, memory systems of the CNS (may be related to Alzheimer's Disease). Most receptors for acetylcholine are ionotropic.
- 20. a. Synthesized from tyrosine synthesized in three steps from the amino acid tyrosine Is the direct precursor to norepinepherine. Enzyme converts tyrosine to L-DOPA Generally involved in regulatory motor activity In the basal ganglia, involved in mood, sensory perception, and attention Schizophrenics have too much dopamine, patients with Parkinson's Disease have too little Amines: 1. Dopamin
- 21. 2. Norepinepherine Synthesized directly from dopamine, and forms the direct precursor to epinepherine. It is synthesized in four steps from tyrosine Also known as noradrenaline Used in the CNS by neurons that project in the cortex, cerebellum, and spinal cord; as such has many uses including sleep/wakefulness regulation Activates sympathetic and parasympathetic neurons in the Autonomic Nervous System •Synthesized
- 22. b. Synthesized from tryptophan 3. Serotonin (5-HT) Synthesized in two steps from the amino acid tryptophan Actual name: 5-hydroxytryptamine (5-HT) Regulates attention and other complex cognitive functions, such as sleep, eating, mood, pain regulation Neurons which use serotonin are distributed throughout the brain and spinal cord Directly implicated in depression (also norepinepherine) Used by metabotropic receptors
- 23. Amino Acids 1.Glutamate (Glu) Most prevalent neurotransmitter in the CNS. Used by more that 50% of neurons Derived from a -ketoglutarate Glutamate is the most important excitatory (EPSP) neurotransmitter, exciting about 90% of the postsynaptic terminals to which it contacts As an excitatory neutrotransmitter, it binds to with ionotropic receptors, causing depolarization by opening Na+ ion channels
- 24. 2. alpha-Aminobutyric Acid (GABA) Synthesized directly from glutamate GABA is the most important inhibitory (IPSP) neurotransmitter Present in high concentrations in the CNS, preventing the brain from becoming overexcited As an inhibitory neutrotransmitter, it binds to both ionotropic and metabotropic receptors. Used by inhibitory interneurons in the spinal cord
- 25. 3.Glycine: Glycine is secreted mainly at synapses in the spinal cord. It is believed to always act as an inhibitory transmitter. 4. Nitric oxide: Nitric oxide is especially secreted by nerve terminals in areas of the brain responsible for long-term behavior and for memory.Therefore this transmitter explain some behavior and memory functions that thus far have defied understanding.
- 26. Large Molecules Neuropeptides Derived from secretory proteins formed in the cell body They are first processed in the endoplasmic reticulum (ER) and are moved to the Golgi apparatus before being secreted as large vesicles and transported down the axon in preparation for exocytosis More than 50 peptides have been isolated in nerve cells. For example, Substance P and enkephalins: Active during inflammation and pain transmission in the PNS
- 28. Chemical synapses Overall: Action potential of presynaptic cell causes release of neurotransmitter into the synaptic cleft Binding of neurotransmitter to postsynaptic cell results in a depolarization at excitatory synapses (an excitatory postsynaptic potential EPSP) or stabilization or hyperpolarization at inhibitory synapses (an IPSP).
- 32. N Ca++ channels
- 36. How vesicle fusion occurs: Reserve pool of vesicles is free in synaptic terminal – but these have to undergo docking and priming to be ready to release Some vesicles are attached to the presynaptic membrane by connections between specific proteins on vesicle and counterparts on presynaptic membrane- at least 6 different proteins are believed to be involved. These are primed. They have joined the ready reserve pool. To enter the ready-to-release pool, a primed vesicle must be docked by becoming associated with n-type Ca++ channels at the presynaptic membrane. Depolarization opens the Ca++ channels – tiny geysers of Ca++ occurs at that vesicle’s location – this Ca++ causes vesicle fusion – transmitter is released into synaptic cleft.