生理学英文版教学课件：24-nervous system-2-2015

1、 Neurotransmitter & Receptor PUMC & CAMS Xue GaoWays of Neurons Communication Definition: Endogenous signaling molecules that are synthesized & liberated by presynaptic neuron into the synaptic cleft, then combine with receptor in postsynaptic neuron or effector cell, cause a specific biological eff

2、ect Neuromodulator: Synthesized & liberated by presynaptic neuron to modulate the effect of neurotransmissionNeurotransmitter Characters that a classical neurotransmitter must be Synthesized by presynaptic neurons Released into synaptic cleft Combine with receptors located at postsynaptic neuron Rem

3、oved in a specific way Have specific Agonist & Antagonist Some substances e.g. CO & NO act as neurotransmitterClassification of neurotransmitter Small-molecule, rapidly acting transmitters Class I: Acetylcholine Class II: Amines Norepinephrine, Epinephrine, Dopamine, Serotonin, Histamine Class III:

4、Amino Acids GABA, Glycine, Glutamate, Aspartate Class VI: NO, CO Large-molecule, slowly acting transmitters Neuropeptide Small-molecule transmitter: In most cases, they are synthesized in the cytosol of presynaptic terminal Most often the effect is to increase or decrease conductance through ion cha

5、nnels The transmitter are continually recycled & used over and over again Large-molecule transmitter: They are synthesized as integral part of large protein molecules by ribosomes in the neuronal cell body The transmitter vesicles are transported all the way to the tip of nerve fiber by axonal strea

6、ming of the axonal cytoplasm at a very slow rate The vesicles is autolyzed & is not reusedSynaptic Vesicles One neuron axon terminal may contain two or more kinds of neurotransmitter in different synaptic vesicles that can be distinguished using the electron microscopeNeurotransmitter Co-existencePK

7、 (Dale Principle)Neurotransmitter Co-existenceNeurotransmitter co-existence Definition: Proteins on the cell membrane or in the cytoplasm that could bind with specific neurotransmitters & alter the behavior of postsynaptic neurons or effector cellReceptorAgonist: A substance that mimics a specific n

8、eurotransmitter, is able to attach to that neurotransmitters receptor & thereby produces the same action that the neurotransmitter usually producesAntagonist (Blocker): A substance that bind to but do not activate receptors, thereby blocking the actions of neurotransmitterLigand of receptor Receptor

9、 quantity & affinity can be changed in different condition Up-regulation Down-regulationRegulation of ReceptorWestern blot According to the “ligand” According to the “location”: Membrane (transmembrane) receptor Cytoplasmic receptor Nuclear receptor Receptor Classification According to -“Mechanism o

10、f Receptor Activation”Receptor Classification Ion Channel-linked Receptor G Protein-Coupled Receptor Enzyme-linked Receptor (6 known types) Presynaptic Receptor (Autoreceptor)Ion Channel-linked Receptor Receptor directly controls channelFast reactionG Protein-Coupled Receptor Receptor indirectly con

11、trols channel (Second Messenger System) 1st Messenger: Neurotransmitter 2nd Messenger: cAMP/cGMP IP3 DAG Ca2+ Slow & Prolonged ReactionG Protein-Coupled ReceptorSome Important Transmitters Acetylcholin Catecholamines Dopamine Norepinerphrine Epinephrine Amino Acids Glutamate (+) GABA (-amino butyric

12、 acid) (-)Acetylcholine (Ach)Ach Synthesis Choline+ Acetyl CoAAch + CoA CholineAcetyltransferaseAch - Distribution Peripheral Nervous System (PNS): Neuro-Muscular junction: Motor neuron innervated the skeletal muscles Preganglionic neurons of autonomic NS Postganglionic neurons of parasympathetic NS

13、 Few postganglionic neurons of sympathetic NS Central Nervous System (CNS) - Widespread Muscarinic Receptors: M Receptor -Subtype: M1M5 Nicotinic Receptors: N Receptor -Subtype: N1 & N2Ach Receptors(Cholinergic Receptor)- Subtype: M1M5 - G Protein-Coupled Receptor- Parasympathetic target organs- Som

14、e sympathetic target organs (Sweat glands, Sympathetic vasodilator nerve)- Antagonist: AtropineMuscarinic Receptors: M ReceptorMuscarine-like action Inhibition of cardiac activity Constriction of bronchial smooth muscle, gastrointestinal smooth muscle, bladder detrusor muscle Increasing of digestive

15、 gland & sweat gland secretion Dilation skeletal muscle vesselAch -Heart EffectMuscarine-like action -Subtype: N1, Neuronal type N2, Muscle type - Ion Channel-linked Receptor - Distribution: N1:Autonomic postganglia N2: Neuromuscular junction (Motor Endplate membrane） - Antagonist: Tubocurarine Nico

16、tinic Receptors: N ReceptorNa+ inflow k+ outflowNicotin-like Action The Life Cycle of AchHenry Hallett Dale Otto Loewi for their discoveries of Ach as neurotransmitter”1936 Nobel Prize in Medicine Dopamine Norepinerphrine EpinephrineCatecholaminesSynthesisCNSCNS & PNSCNSDopamine (DA) Receptor: D1D5

17、All are G Protein-Coupled Receptor Mainly involved in Somatic movement， emotion，cardiovascular activity，et al Epinephrine Mainly involved in cardiovascular activityNorepinephrine (NE) Found both in PNS & CNS PNS: -Postganglionic neurons of sympathetic nerve CNS:-Regulation of General Behavior, e.g.

18、Cardiovascular Activity, Body TemperatureAll receptors are G Protein-Coupled ReceptorConstriction of Vessel & uterus Relaxation of small intestine Relaxation of Vessel & uterus, small intestine, bronchial Exciting Cardiac activity Excitatory Amino Acid Glutamate / Glutamic Acid (Glu)Glutamate Synthe

19、sis Amino Acid NeurotransmitterGlutamate ReceptorIon Channel-linked Receptor G-protein Linked Receptor EAATs： Excitatory Amino Acid Transporters VGLUTs： Vesicular Glutamate Transporters xCT： Glutamate-Cystine exchangerGlutamate TransportersNMDA ReceptorCa2+/Na+ Mg+ is voltage-dependant blocker Quant

20、ity & location at the postsynaptic membrane is relative stable Induce Slow & Prolonged postsynaptic membrane depolarization reaction Ca2+ is the main inflow ionCharacters of NMDA ReceptorAMPA Receptor Na+/Ca2+ Na+ is the mail inflow ion Induce Fast Postsynaptic Membrane Depolarization Reaction Have

21、the property of desensitization quickly Quantity & location at the postsynaptic membrane is unfixed Characters of AMPA Receptor Wandering Receptor AMPA receptor AMPA receptors can move between an intracellular pool and the neuronal surface by the processes of exocytosis and endocytosis AMPA receptor

22、s can also move by lateral diffusion in the plasma membrane until they are captured and immobilized by putative anchoring proteins concentrated in postsynaptic regions AMPA receptors are also immobilized by increases in intracellular calcium levelsWay of AMPA-R WonderingChinese Restaurant SyndromeMS

23、G: Monosodium GlutamateReaction Process of Ionotropic Glutamate Receptor Synaptic Plasticity Definition: Repeated activity of synapse may induce the long term change of synaptic morphology & function or synaptic transmission efficiency iGluRs may be involved in long term synaptic plasticity, includi

24、ng: Long term potential (LTP) Long term depression (LTD) Definition: is a long-lasting enhancement in “amplitude of postsynaptic potential” (synaptic strength) LTP is widely considered one of the major cellular mechanisms that underlies “learning & memory”Long Term Potential (LTP) -(NMDAR/AMPAR & LTP)LTP mechanism Definition: is a long lasting reduction in synaptic strength LTD is thought to result mainly from a decreas