Action Potential Propagation

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Action Potential Propagation Interneuronal Communication pre-class video Sue Keirstead, Ph.D. Assistant Professor Dept. of Integrative Biology and Physiology Stem Cell Institute E-mail: sakeir@umn.edu Tel: 612 626 2290 Class 6: Action Potentials – Learning Objectives 1. Explain how a receptor potential in a sensory neuron can lead to the initiation of an action potential at the trigger zone of the sensory axon. 2. Compare and contrast the properties of mechanically-gated channels and voltage- gated channels (consider what causes them to open and close, where they are located, what kind of membrane potentials they mediate). 3. Compare and contrast the properties of voltage-gated Na+ and voltage-gated K+ channels, and understand how voltage influences their activation and inactivation (do they both have inactivation gates?). 4. Understand how the activity of voltage-gated Na+ and K+ channels generates an action potential and the roles of these channels in each phase of the action potential (i.e. depolarization/rising phase, overshoot, repolarization, afterhyperpolarization/undershoot). 5. Explain how action potentials are propagated along an axon and compare this to the passive conduction like the local current flow in dendrites. 6. Compare the distribution of ion channels along unmyelinated versus myelinated axons and explain how this accounts for the difference in conduction velocity between these two types of axons. Predict the effects on action potential propagation of demyelinating diseases, such as multiple sclerosis. 7. Understand how stimulus intensity is encoded by neurons. Why do we need Right side of brain Left side of brain to have action Cerebral cortex potentials? 1 Brain Interneuron Upper motor neuron 2 Thalamus Interneuron Sensory neuron 3 Spinal cord 4 Key: Graded potential Sensory Axon action potential receptor 6 5 Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Current flow within an axon is decremental due to loss of current through leak channels ECF ICF ECF Propagation of the Action Potential Plasma Membrane Key: ECF Resting membrane potential Depolarizing phase of AP Plasma membrane Repolarizing phase of AP After-hyperpolarization phase of AP Na+ ICF K+ ECF Time Na+ ICF K+ K+ ECF Na+ ICF Figure 7.23 Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. Continuous conduction (unmyelinated axons) Cell body Time Na+ 1 msec Na+ Current flow due to Trigger zone opening of Na+ channels Na+ 5 msec Na+ Na+ 10 msec Na+ Leading edge of action potential Saltatory conduction (myelinated axons) Cell body Time Nodes of Ranvier Na+ 1 msec Na+ Current flow due to opening of Na+ Trigger zone channels Na+ 5 msec Na+ Na+ 10 msec Na+ Leading edge of action potential Continuous vs Saltatory Conduction CT 3.2 The purpose of propagating action potentials down the axon is to trigger neurotransmitter release from the axon terminal 1 Presynaptic axon Action potential 2+ 2 Ca Voltage-gated Ca2+ Ca2+ 2 channel Synaptic vesicles 8 Synaptic cleft Ca2+ Neurotransmitter 3 Na+ Neurotransmitter receptor: 4 Neurotransmitter binding site Ion channel 5 7 Local current flow Postsynaptic neuron 6 Postsynaptic potential Figure 7.26 Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved. .

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Action Potential and Synapses
SENSORY RECEPTORS RECEPTORS GATEWAY TO THE PERCEPTION AND SENSATION Registering of inputs, coding, integration and adequate response PROPERTIES OF THE SENSORY SYSTEM According the type of the stimulus: According to function: MECHANORECEPTORS Telereceptors CHEMORECEPTORS Exteroreceptors THERMORECEPTORS Proprioreceptors PHOTORECEPTORS interoreceptors NOCICEPTORS STIMULUS Reception Receptor – modified nerve or epithelial cell responsive to changes in external or internal environment with the ability to code these changes as electrical potentials Adequate stimulus – stimulus to which the receptor has lowest threshold – maximum sensitivity Transduction – transformation of the stimulus to membrane potential – to generator potential– to action potential Transmission – stimulus energies are transported to CNS in the form of action potentials Integration – sensory information is transported to CNS as frequency code (quantity of the stimulus, quantity of environmental changes) •Sensation is the awareness of changes in the internal and external environment •Perception is the conscious interpretation of those stimuli CLASSIFICATION OF RECEPTORS - adaptation NONADAPTING RECEPTORS WITH CONSTANT FIRING BY CONSTANT STIMULUS NONADAPTING – PAIN TONIC – SLOWLY ADAPTING With decrease of firing (AP frequency) by constant stimulus PHASIC– RAPIDLY ADAPTING With rapid decrease of firing (AP frequency) by constant stimulus ACCOMODATION – ADAPTATION CHARACTERISTICS OF PHASIC RECEPTORS ALTERATIONS OF THE MEMBRANE POTENTIAL ACTION POTENTIAL TRANSMEMBRANE POTENTIAL
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Pain-Enhancing Mechanism Through Interaction Between TRPV1 and Anoctamin 1 in Sensory Neurons
Pain-enhancing mechanism through interaction between TRPV1 and anoctamin 1 in sensory neurons Yasunori Takayamaa, Daisuke Utab, Hidemasa Furuec,d, and Makoto Tominagaa,d,1 aDivision of Cell Signaling, Okazaki Institute for Integrative Bioscience, Okazaki 444-8787, Japan; bDepartment of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan; cDivision of Neural Signaling, National Institute for Physiological Sciences, Okazaki 444-8787, Japan; and dDepartment of Physiological Sciences, Graduate University for Advanced Studies, Okazaki 444-8787, Japan Edited by David Julius, University of California, San Francisco, CA, and approved March 20, 2015 (received for review November 11, 2014) The capsaicin receptor transient receptor potential cation channel channels. Mammalian TRPV1 is activated by noxious heat, acid, and vanilloid 1 (TRPV1) is activated by various noxious stimuli, and the many chemical compounds including capsaicin (16–18). The calcium stimuli are converted into electrical signals in primary sensory permeability of TRPV1 is more than 10 times that of sodium, neurons. It is believed that cation influx through TRPV1 causes suggesting that TRPV1 could activate anoctamins readily, leading depolarization, leading to the activation of voltage-gated sodium to further depolarization. ANO1 plays an important role in noci- channels, followed by the generation of action potential. Here we ception in primary sensory neurons (19), and bradykinin-induced report that the capsaicin-evoked action potential could be induced and neuropathic pain-related behaviors were reduced in ANO1 by two components: a cation influx-mediated depolarization caused conditional-knockout mice (20, 21), suggesting that interaction be- by TRPV1 activation and a subsequent anion efflux-mediated de- tween the two proteins could strongly enhance nociceptive signals.
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The Basic Hypothesis for Mechanotransduction in Sensory Receptors
Trakia Journal of Sciences, Vol. 17, Suppl. 2, pp 22-26, 2019 Copyright © 2019 Trakia University Available online at: http://www.uni-sz.bg ISSN 1313-3551 (online) doi:10.15547/tjs.2019.s.02.006 THE BASIC HYPOTHESIS FOR MECHANOTRANSDUCTION IN SENSORY RECEPTORS Ch. Chouchkov, Iv. Maslarski* Department of Anatomy, Histology, Pathology and Forensic Medicine, Faculty of Medicine, SU “St. Kliment Ohridski”, Sofia, Bulgaria ABSTRACT One of the most involving problem in the nerve tissue organization is the process of information transduction in the sеnsory receptors and the associated with them sensory cells. The aim of the present report is to review and discuss the data during the latter twenty years about the localization of molecules recently localized in different structural elements of sensory corpuscles and their possible role in the process of mechanotransduction. The most important obligatory parts in the process of mechanotransduction of all sensory receptors are their non-myelinated parts and their bulbous ends or so called nerve endings, like Pacinian and Meissner corpuscles, Krauses bulb, Golgi-Mazzoni corpuscle and Merkel disk. In conclusion, it is still a matter of elucidation in the future to precisely localize the proteins making up the mechanosensitive ion channels. There also exist difficulties regarding the correlation of the physiological with morphological data due to the fact that the receptor axolemma is surrounded by complex cellular structures whose isolation is hard to perform. Key words: Merkel disk, Pacinian corpuscle, Schwann inner core complex, neurotransmission INTRODUCTION mechanotransduction. The sensory receptors, One of the most intriguing problem in the responsible for the process of nerve tissue organization is the process of mechanotransduction are designed as information transduction in the sеnsory mechanoreceptors.
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Neurotransmission
Neurotransmission Prof. Dr. Szabolcs Kéri University of Szeged, Faculty of Medicine, Department of Physiology 2021 Why studying synapses? Synaptopathy: diseases of the brain characterized by pathological synaptic structure and function Key points 1. Synapsis: definition and classification 2. Signal transduction in the synapsis 3. Neurotransmitters: definition and classification 4. Important transmitter systems and their functions 5. Non-conventional transmission: axon – glial connection, retrograde signals, and volume transmission 1. Definition and classification of synapses Definition and classification of synapses Synapsis: Axons do not form a continuous network. They make contacts with dendrites or cell bodies. Synapse is a connection point to pass electrical or chemical signals to another neuron or to a target cell. A. CHEMICAL (neurotransmitter and receptor) B. ELECTRIC (gap junction) I. Connection type: II. Transmitter type and function: • Axodendritic • Excitatory (Gray I: asymmetric, glutamate, spherical • Axosomatic vesicles) • Axoaxonal • Inhibitory (Gray II: symmetric, GABA, oval vesicles) • Axomyelinic • Modulatory (monoamines, small dense core vesicles) • Peptides (large dense core vesicles) Spine Clear vesicles Spine synapse Dense core vesicles Shaft snapse Gray I Gray II Asymmetric Symmetric Glutamate GABA Axodendritic Axoaxonal Posztszinaptikus Axosomatic Postsynapticdenzitás (PSD)density (PSD) Outlook: molecular diversity of the synapses 2. Signal transduction in the synapse Electric synapses: comparison with chemical synapses ELECTRIC • Connexon pore (6 connexins) • Bidirectional diffusion of small molecules • Fast: minimal synaptic delay • Synchronization of neuronal groups • Glial networks • Passing second messengers (cAMP) CHEMICAL • No pore in the membrane (transmitter and receptor needed) • Synaptic delay (1-1.5 ms) • One-way (pre → postsynaptic) Chemical neurotransmission 1. Transmitter stored in vesicles 2. 2. Action potential at the presynaptic terminal 1.
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Educational Research Applications Detwiler PB., Educ Res Appl: ERCA-138 Review Article DOI: 10.29011/2575-7032/100038 Sensory Transduction: a Common Blue Print
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Optical Assessment of Nociceptive TRP Channel Function at the Peripheral Nerve Terminal
International Journal of Molecular Sciences Review Optical Assessment of Nociceptive TRP Channel Function at the Peripheral Nerve Terminal Fernando Aleixandre-Carrera 1 , Nurit Engelmayer 2,3, David Ares-Suárez 1, María del Carmen Acosta 1 , Carlos Belmonte 1, Juana Gallar 1,4,Víctor Meseguer 1,*,† and Alexander M. Binshtok 2,3,† 1 Instituto de Neurociencias, Universidad Miguel Hernández—CSIC, 03550 San Juan de Alicante, Spain; f.aleixandre@umh.es (F.A.-C.); dares@umh.es (D.A.-S.); mcarmen.acosta@umh.es (M.d.C.A.); carlos.belmonte@umh.es (C.B.); juana.gallar@umh.es (J.G.) 2 Department of Medical Neurobiology, Institute for Medical Research Israel—Canada, Hadassah School of Medicine, The Hebrew University, Jerusalem 91123, Israel; nurit.engelmayer@mail.huji.ac.il (N.E.); alexander.binshtok@mail.huji.ac.il (A.M.B.) 3 The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel 4 Instituto de Investigación Sanitaria y Biomédica de Alicante, 03550 San Juan de Alicante, Spain * Correspondence: vmeseguer@umh.es † Shared last authorship. Abstract: Free nerve endings are key structures in sensory transduction of noxious stimuli. In spite of this, little is known about their functional organization. Transient receptor potential (TRP) channels have emerged as key molecular identities in the sensory transduction of pain-producing stimuli, yet the vast majority of our knowledge about sensory TRP channel function is limited to data obtained from in vitro models which do not necessarily reﬂect physiological conditions. In recent years, the development of novel optical methods such as genetically encoded calcium indicators and photo-modulation of ion channel activity by pharmacological tools has provided an invaluable Citation: Aleixandre-Carrera, F.; opportunity to directly assess nociceptive TRP channel function at the nerve terminal.
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