Synaptic Transmission PDF

Synaptic Transmission Instructors : Dr. Talay Yar email: [email protected] Dr. Mona Alsheikh email: [email protected] Department of Physiology Tuesday, November 28, 2023 03.2.11 014 0 531 damn animi Learning Objectives june 5 Yum again 12:43 iii AI 051 is After participating successful...

Synaptic Transmission Instructors : Dr. Talay Yar email: [email protected] Dr. Mona Alsheikh email: [email protected] Department of Physiology Tuesday, November 28, 2023 03.2.11 014 0 531 damn animi Learning Objectives june 5 Yum again 12:43 iii AI 051 is After participating successfully in this session and related activities, you should understand: am  The Physio-anatomy of a synapse (chemical, electrical)  General concepts of neurotransmitter production, release, function and inactivation at the synapse  Major types of neurotransmission  Most common excitatory and inhibitory neurotransmitters in the CNS  Excitatory neurotransmitter receptors and the ions involved, ionotropic and metabotropic receptors, excitatory post-synaptic potentials (EPSPs)  Inhibitory neurotransmission, the ions involved and the role of membrane potential, inhibitory post-synaptic potentials (IPSPs)  How the activation of receptors by neurotransmitters is translated into a response.  Longer term implications of neurotransmitter actions Tuesday, November 28, 2023 Synaptic Transmission 2 13:01 Why is This Rhino Not Resisting? F paralysis is 24 ima will blockthem Lead toblocking neuromuscular the junction Tuesday, November 28, 2023 Synaptic Transmission 3 12:43 Here we start Synapse  a structure that allows transmission of an electrical or chemical signal to another cell  Typically: junctions between ‘presynaptic’ & ‘post synaptic’ neurons Tuesday, November 28, 2023 Synaptic Transmission synapse pre post 4 12:43 But a neuron may terminate on another neuron or a muscle, a gland. neuron gland neuroglandular neuron Tuesday, November 28, 2023 muscle neuromuscular Synaptic Transmission 5 12:43 Types of Synapses  Chemical synapses transmit signals indirectly using chemical transmitters that bind with receptors and open ion channels to it napses change membrane potential of the receiving cell. neuromuscularjuncti  Electrical synapses transmit signal directly through gap 1 junctions to the receiving cell. They are rare in humans. I muse much fasterThereisno transmitter uro thesignal two directions cause thereisnoreceptors Tuesday, November 28, 2023 Synaptic Transmission 6 12:43 A neuron communicates with the target cell in a chemical synapse  through NEUROTRANSMITTER, that ‘transmits’ the excitation of a ‘NEURON’ to the target cell (muscle, gland or another neuron) and brings a change in that. IEii i iiI thereleaseotthen.cn depend the presynaptic terminals onnowmuncanciamenters Tuesday, November 28, 2023 iiiiiii.iti.i i I If Synaptic Transmission 7 Transmission at a chemical synapse vesicle of terminals presynaptic transmitter (tx) pre tx-R operated I channel post release [Ca2+] fatagegatet have Axon forktandNat channels Ca2+ +++ +++ Na+ Na+, Transmitter APpre channels open lead to 00 [Ca] enter Tuesday, November 28, 2023 channels tx release V-G Ca2+ V-G Na+ K+, Ca++ 0 diffuse <20 nm> 0.5 ms open tx-R depolarization APpost 12:43 Neurotransmitters transmitter IE S'vecellbody cellbody daxonterminal11 Endorphins Axonterminal 51 left ja Acetylcholine Example: Acetylcholine  Synthesized & stored in the presynaptic neuron.  Released in response to excitation (action potential) of presynaptic neuron.  Bind with receptors on the postsynaptic cell & open ion channels that leads to 1action – excitation OR Thereiseach ooots – inhibition of the 100th postsynaptic cell. µ Potential Jg lineachneuroy Tuesday, November 28, 2023 Synaptic Transmission 9 fifteen zymewillavoid Peomenantstimulation Tuesday, November 28, 2023 12:43 Removal of Neurotransmitter from Synaptic Cleft Neurotransmitter can be returned to axon terminals for reuse Enzymes inactivate neurotransmitters 0 Neurotransmitters 0 Tuesday, November 28, 2023 Synaptic Transmission Can diffuse out of the synaptic cleft to the blood 1 1 Ligands and Receptors????  A ligand is any substance that binds to a receptor!  Receptors are often named and classified largely by reference to the ‘ligand’.  Acetylcholine and norepinephrine are ‘physiological’ ligands, i.e. provided by the body.  Receptors are often subdivided by reference to ligands e.g., ACh into nicotinic (nACh) and muscarinic (mACh) receptors.  Nicotine stimulates nACh receptors.  Muscarine stimulates mACh receptors Tuesday, November 28, 2023 in CNS PNS neuro muscularjunction inCNSPNS glans smoothmuscles 12:43 Steps of Synaptic Transmission Step-1: Excitation (Action Potential) in presynaptic Neuron Step-2: Opening of Voltage gated Calcium Channels & Influx of Calcium into Presynaptic Neuron Step-3: Neurotransmitter release into the synaptic cleft. Calcium Causes release of Neurotransmitters from synaptic vesicles (after binding with a protein synaptotagmin and activating a set of proteins called SNAREs) IStep-4: Neurotransmitter binds to the membrane receptor on the postsynaptic cell. This then leads to Response. This may be: Fast Response through ionotropic receptor OR Slow Response through metabotropic receptor (& G Protein) Step-5-7: Removal of Neurotransmitter & finishing of its effect by: • Reuptake by presynaptic cell • Enzymatic destruction • Diffusion in interstitial fluid Tuesday, November 28, 2023 Synaptic Transmission 13 12:43 Explanation of Step 4 Types of postsynaptic receptors Synaptic Transmission Tuesday, November 28, 2023 14 Explanation of Step 4 12:43 Fast Response of Post Synaptic Cell if moss g Fast response involves ionotropic receptors The neurotransmitter binds to a channel-linked receptor. All channel-linked receptors are ligand-gated channels. The channel opens, the ions flow down their electrochemical gradients, and produce a brief change in membrane potential called a postsynaptic potential (PSP). Postsynaptic potential can be Excitatory (EPSP) or Inhibitory (IPSP) I Tuesday, November 28, 2023 Synaptic Transmission 15 neurotransmit HITH Explanation of Step 4 12:43 Slow Response of Postsynaptic Cell Slow responses act by time but Longer triggering biochemical changes through G protein-linked receptors called metabotropic receptors. Activation of the G protein may either open or close an ion channel. The final effect depends upon the type of ion channel. excitation respons thresh If the result is a depolarization the response is excitation (EPSP) If the result is hyperpolarization the effect is inhibition (IPSP) Tuesday, November 28, 2023 Synaptic Transmission Tey mi mi Ii jitsu 55 16 12:43 Excitatory Neurotransmitters & EPSP Tuesday, November 28, 2023 Synaptic Transmission 17 12:43 Inhibitory Neurotransmitters & IPSP I Tuesday, November 28, 2023 Synaptic Transmission 18 12:43 Neurotransmitters- EPSPs & IPSPs  An excitatory synapse causes a graded potential that depolarizes the membrane and brings it closer to threshold.  The depolarization is an excitatory postsynaptic potential (EPSP) (may be fast or slow).  At inhibitory synapses the neurotransmitter opens channels for either K+ or Cl-. Opening K+ channels causes K+ to leave the cell leading to hyperpolarizing the membrane (making more negative) and creating an Inhibitory post-synaptic potential (IPSP).  Likewise opening of Cl- channels causes movement of Cl- into the cell leading to hyperpolarization of cell membrane and creating an Inhibitory post-synaptic potential (IPSP). Tuesday, November 28, 2023 Synaptic Transmission 19 12:43 Some Important Neurotransmitters Neurotransmitter Examples of location Examples of interest the Neuromuscular Junction Parasympathetic NS Myasthenia Gravis Peptic Ulcer Noradrenaline Sympathetic nervous System Flight & Fright response Blood Vessels Gastric Secretion Anaphylaxis Peptic Ulcer Acetylcholine neurotransmitter important most Controls the integrative functions of the nervous system : thinking ,judgment ,memory ,intelligence Histamine Me 5TH Dopamine Substantia Nigra (Basal Ganglia) Parkinson’s Disease Serotonin Locus ceruleus in brain Mood & Behaviour Depression GABA Presynaptic Inhibition moti minion Cause drowsiness Tuesday, November 28, 2023 Synaptic Transmission 20 12:43 Some Important Neurotransmitters Excitatory Or Inhibitory (Depending on the receptor)  Acetylcholine Excitatory only  Glutamate  Aspartate  Noradrenaline Inhibitory only  Dopamine  GABA  Serotonin  Glycine  Histamine Tuesday, November 28, 2023 Synaptic Transmission 21 12:43 Example of Excitatory Neurotransmitter Acetylcholine at Neuromuscular Junction Tuesday, November 28, 2023 Synaptic Transmission 22 Example of Inhibitory Neurotransmitter Tuesday, November 28, 2023 Synaptic Transmission 23 Sites or steps of Synaptic Transmission that can be altered or be a target of disease or drugs Synthesis of NT – (Precursors) Storage of NT in vesicles Release of NT (Stimulation) Release of NT (inhibition) (stimulation of autoreceptors) Release of NT (Stimulated) (blocking autoreceptors) Release of NT (Inhibition) I Postsynaptic receptors - Stimulation Reuptake of NT Inactivation of NT - enzyme Postsynaptic receptors - Blocking 24 ٥/١٦/١٤٤٥ Tuesday, November 28, 2023 Synthesis of NT - Enzymes 12:43 Modification of Synaptic Transmission in Treatment of Diseases Inactivates enzymes synthesizing NT Acts as Precursor of NT Prevents Storage of NT in vesicles Inhibits release of NT by stimulating autoreceptors sinf Stimulates release of NT Inhibits release of NT Stimulates postsynaptic receptors posts Tuesday, November 28, 2023 Blocks reuptake of NT f Blocks postsynaptic receptors Increases release of NT by blocking autoreceptors wife Synaptic Transmission Inactivates enzyme deactivating NT PCPA:para-Chlorophenylalaninie 25 Environmental Changes and Synaptic Transmission  Acidosis. – depresses neuronal activity. examples– diabetic coma – pH change from 7.4 to 7.0 usually will induce coma. o  Alkalosis. – increases neuronal excitability. example_ – epileptic attack – pH change from 7.4 to 8.0 usually will induce seizures.  Hypoxia. 5 – brain highly dependent on oxygen – interruption of brain blood flow for 3 to 7 sec can lead to unconsciousness. Tuesday, November 28, 2023 12:43 i How can Synaptic Transmission be altered? Synthesis of NT Precursor of NT Synthesis of NT (Enzymes) Release of NT (inhibition) (stimulation of autoreceptors) Storage of NT in vesicles Release of NT (Stimulation) Release of NT (Stimulated) (blocking autoreceptors) Release of NT (Inhibition) Reuptake of NT Stimulation of postsynaptic receptors Inactivation of NT (enzyme) Blocking of postsynaptic receptors Tuesday, November 28, 2023 Synaptic Transmission 30 12:43 Working of a Chemical Synapse Steps 1-7 are summarized in the next slide Tuesday, November 28, 2023 Synaptic Transmission 29 12:43 Synapse Chapter 4 Page numbers 111 to 122 Introduction to Human Physiology, 8th edition. Lauralee Sherwood, 2013 Tuesday, November 28, 2023 Propagation of Action Potential 12:43 Thank You iÉ Tuesday, November 28, 2023 miss Synaptic Transmission 28