* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download www.invertebrate.us
Survey
Document related concepts
Node of Ranvier wikipedia , lookup
Biochemical cascade wikipedia , lookup
Killer-cell immunoglobulin-like receptor wikipedia , lookup
Lipid signaling wikipedia , lookup
Glutamate receptor wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Paracrine signalling wikipedia , lookup
Purinergic signalling wikipedia , lookup
VLDL receptor wikipedia , lookup
Leukotriene B4 receptor 2 wikipedia , lookup
Signal transduction wikipedia , lookup
Transcript
Chapter 8 Part 4 Neurotransmitters Neurotransmitter Synthesis – Occurs either in cell body or axon terminal – Axon terminal lacks organelles for protein synthesis – Polypeptide/protein neurotransmitters and enzymes must be made in the cell body and transported to the axon terminal – Enzymes move by slow axonal transport – Neurotransmitters move by fast axonal transport Neurotransmitter Release (Fig. 8-21, p. 275) When an AP reaches the axon terminal – Voltage-gated Ca++ channels open – Ca++ ions move into the cell (axon terminal) – Ca++ ions bind to regulatory proteins and initiate exocytosis – Synaptic vesicle fuses with cell membrane – Fused area opens, neurotransmitter (inside synaptic vesicle) moves out into the synaptic cleft – Diffuses across the cleft – Binds with a receptor on the other side – Binding initiates a response Figure 8-21, overview Copyright © 2010 Pearson Education, Inc. Neurocrine Signal Molecules (p. 275) These are stored in the synaptic vesicles of the axon terminal Include neurotransmitters, neuromodulators and neurohormones Chemical composition is varied “The number of molecules identified as neurotransmitters and neuromodulators is large and growing daily” 3 kinds of Neurocrines Neurotransmitters – Rapid effect – Diffuses across a synapse to a target cell Neuromodulators – Slow effect – Acts either on cell which secreted it or on neighboring cells Neurohormones – Once released by neuron, these diffuse into the blood Neurotransmitters and Neuromodulators can act as either: Paracrine Signals – Target cells are located close to the neuron which secreted these or Autocrine signals – Act on the cell that secreted them “The array of neurocrines in the body is truly staggering” (p. 275) See Table 8-4, p. 276 7 classes of neurocrines (based on structure): 1. Acetylcholine 2. Amines 3. Amino Acids 4. Peptides 5. Purines 6. Gases 7. Lipids Table 8-4, part 1 Copyright © 2010 Pearson Education, Inc. Table 8-4, part 2 Copyright © 2010 Pearson Education, Inc. Table 8-4, overview Copyright © 2010 Pearson Education, Inc. 1. Acetylcholine (ACh) Neurons that secrete ACh and receptors that bind ACh are called cholinergic Myasthenia gravis: disease in which the immune system fails to reecognize (as self) the ACh receptors of skeletal muscle (p. 278) 2. Amines All active in the CNS Norepinephrine is the major neurotransmitter in the PNS 2. Amines (continued) Each of these are derived from a single amino acid Example: tyrosine can be converted to dopamine, or norepinephrine, or epinephrine These 3 can be neurotransmitters or neurohormones (when secreted by adrenal medulla) drenergic or noradrenergic Neurons that secrete norepinephrine 2. Amines (continued) This name (adrenergic) comes from the early 20th century British researchers. They thought that sympathetic neurons secreted adrenaline (epinephrine) and so named the neurons adrenergic Serotonin (5-hydroxytryptamine or 5-HT) Another amine neurotransmitter Made from the amino acid tryptophan Serotonergic neurons—secrete serotonin Table 8-4, part 1 Copyright © 2010 Pearson Education, Inc. 2. Amines (continued) Histamine Another amine neurotransmitter Made from the amino acid histadine 3. Amino Acids At least 4 function as neurotransmitters in the CNS: Glutamate (glutaminergic neuron/receptor): primary excitatory neurotransmitter (CNS) Aspartate: same function as glutamate in selected brain regions 3. Amino Acids (continued) GABA (gamma-aminobutyric acid): Main inhibitory neurotransmitter in the brain Glycine: Primary inhibitory neurotransmitter in the spinal cord Also, potentiates (see next slide) the excitatory effects of glutamate at one type of glutamate receptor Figure 7-18 Synergism or Potentiation (p. 234) The combined effects are greater than the sum of the individual actions Copyright © 2010 Pearson Education, Inc. Agonist A molecule that combines with a receptor and mimics a response Antagonist: One substance opposes the action of another For more details, see p. 395 and Table 11-3 4. Peptides Lots of different neurotransmitters and neuromodulators are peptides: Substance P: involved in some pain pathways Opioid peptides (enkephalins and endorphins): These mediate pain relief or analgesia Cholecystokinin (CCK) and Atrial natriuretic peptide Function as both neurohormones and neurotransmitters 5. Purines Adenosine Adenosine monophosphate (AMP) Adenosine triphosphate (ATP) All 3 above can act as neurotransmitters They bind to purinergic receptors in the CNS and also in the heart 6. Gases Nitric Oxide (NO) An unstable gas, synthesized from oxygen and the amino acid arginine When acting as a neurotransmitter, it diffuses freely into a cell rather than bind to a membrane receptor Once inside the cell, it binds to a protein Has a half-life of 2-30 seconds, very hard to study Can also be released by cells other than neurons, acts as a paracrine in this case 6. Gases (continued) Carbon monoxide (CO) and hydrogen sulfide (H2S) Recent work has shown that these two toxic gases are produced in tiny amounts in the body to serve as neurotransmitters 7. Lipid Neurocrines Eicosanoids (p.31) are 20-carbon fatty acids, found in animals Eikos = twenty Eicosanoids are regulators of various physiological functions Examples: Thromboxanes, leukotrienes, prostaglandins 7. Lipid Neurocrines (continued) Several eicosanoids are endogenous ligands for cannabinoid receptors Endogenous: “originates within” CB1 cannabinoid receptor is found in the brain CB2 cannabinoid receptor is found on immune cells The receptors were named for one of their endogenous ligands: THC which comes from the plant Cannabis sativa or marijuana Multiple Receptor Types All neurotransmitters (except NO) bind to one or more receptor types Each receptor type may have multiple subtypes, allowing one neurotransmitter to to have different effects in different tissues Receptor subtypes are distinguished by letter and number subscripts Multiple Receptor Types Receptor subtypes are distinguished by letter and number subscripts: Serotonin (5-HT) has at least 20 receptor subtypes: 5-HT1A 5-HT4 etc. Membrane Receptor Categories (p. 182) Neurotransmitter receptors are of two types: Ligand-gated ion channels And G protein-coupled receptors (GPCR) Lots of current research on both of these (see p. 279 for details) Figure 6-5 Copyright © 2010 Pearson Education, Inc. Ionotropic receptors These alter ion channel function Metabotropic receptors These work through second-messenger systems Some metabotropic GPCRs regulate opening and closing of ion channels Agonist A molecule that combines with a receptor and mimics a response Antagonist: One substance opposes the action of another For more details, see p. 395 and Table 11-3 Cholinergic receptors (2 main types) Nicotinic – Nicotine is an agonist for this one – Found on skeletal muscle, in the autonomic division of the PNS, also found in the CNS – Receptors are monovalent cation channels (Na+, K+) – Na+ entry into cells here exceeds K+ entry Cholinergic receptors (2 main types) Muscarinic – Muscarine (from fungi) is an agonist for this one – 5 related subtypes – All are coupled to G proteins and linked to second messengers – Tissue response varies with receptor subtype – Occur in CNS and in autonomic parasympathetic division of PNS Adrenergic receptors – Two classes: alpha and beta, multiple subtypes – All are coupled to G proteins and linked to second messengers – The two classes, alpha and beta, work through different second messenger pathways Glutaminergic receptors – Glutamate is the main excitatory neurotransmitter in the CNS – Action of glutamate at a particular synapse depends on the receptor type on the target cell – AMPA receptors » Ligand-gated monovalent cation channels (similar to nicotinic acetylcholine channels) Glutaminergic receptors (continued) – Action of glutamate at a particular synapse depends on the receptor type on the target cell – NMDA receptors – These are unusual – Cation channels (for Na+, K+, Ca++) – Channel opening requires both glutamate binding and change in membrane potential – At RMP, channel is blocked by a Mg++ ion Postsynaptic responses Fast synaptic potential – Neurotransmitter binds to and then opens a receptorchannel on the postsynaptic cell – This leads to ion movement and a change in membrane potential – Excitatory postsynaptic potential (EPSP) – Depolarizing, more likely to fire an AP – Inhibitory postsynaptic potential (IPSP) – Hyperpolarizing, less likely to fire an AP Slow synaptic potential Use second messengers, therefore, take longer to create the response Also, the response lasts longer In addition to working on ion channels, these responses may modify existing cell proteins or regulate the production of new cell proteins Found in growth and development of neurons and may be a mechanism in long-term memory Figure 8-23 Copyright © 2010 Pearson Education, Inc. Neurotransmitter Activity is rapidly terminated Neurotransmitters, once they cross the cleft and bind, can then be recycled or reused See next two slides Figure 8-22, overview Copyright © 2010 Pearson Education, Inc. Figure 8-24, overview Copyright © 2010 Pearson Education, Inc. Integration of Neural Information Transfer Divergence (Fig. 8-25a, p. 282) – When a presynaptic neuron branches and its collaterals synapse on to multiple target neurons Convergence (Fig. 8-25b, p. 282) – When a group of presynaptic neurons provide input to a smaller number of postsynaptic neurons Combinations of the above (in the CNS) can result in one postsynaptic neuron with synapses from 10,000+ presynaptic neurons Figure 8-25 Copyright © 2010 Pearson Education, Inc. Figure 8-26 Copyright © 2010 Pearson Education, Inc. Spatial Summation (Fig. 8-28a) – Initiation of an AP from several nearly simultaneous graded potentials Temporal Summation (Fig. 8-29) – Summation that occurs from graded potentials overlapping in time Figure 8-28a, overview Copyright © 2010 Pearson Education, Inc. Postsynaptic inhibition (Fig. 8-28b) – A presynaptic neuron releases an inhibitory neurotransmitter onto a postsynaptic cell and alters its response Figure 8-28b, overview Copyright © 2010 Pearson Education, Inc. Temporal Summation (Fig. 8-29) – Summation that occurs from graded potentials overlapping in time Figure 8-29 Copyright © 2010 Pearson Education, Inc. Figure 8-31a, overview Copyright © 2010 Pearson Education, Inc. Figure 8-31b, overview Copyright © 2010 Pearson Education, Inc.