DOCSLIB.ORG

Cell Membrane Potential Resting Membrane Potential

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cell Membrane Potential Resting Membrane Potential Cell Membrane Potential Resting Membrane Potential • Resting membrane potential: for quiescent cells The genesis of resting potential is mainly the result of • Action (membrane) potential: excited cells • The concentrations of diverse ions which prevail inside and outside of the cell close to the surface of the Both resting and action potentials are produced by temporary changes in the current flow across the membrane. membrane, namely, in the ionic flow through the resting and gated channel proteins in the membrane. • The selective permeability of the cell membrane to particular ions. Each and every biosignal has its origin in a brief imbalance of the resting membrane potential, irrespective of the biosignal’s type. Basic Biophysics Tools and Relationships Resting Potential of a Membrane Permeable to One Ion 11.4.1 Basic Laws J J (diffusion) J (drift) 0 -Fick’s Law: diffusion Einstein Relationship K kT [K ] d[I] D kT o E vi vo ln EK+: Nernst potential J D K q [K ] dx q i Same for Na+ and Cl- -Ohm’s Law: drift (: mobility, Z: ionic valence, [I] ion concentration) dVm Donnan Equilibrium J Z[I] - Suppose a membrane is permeable to both K+ and Cl-. dx [K ]o [Cl ]i E E K Cl [K ]i [Cl ]o Goldman Equation - The Goldman equation describes the relationship between Vm and permeable ions. - Valid when the membrane potential or electric field is constant. (good for resting potential) qV V KKe kT K oi J qV K kT e 1 qV V Na Na e kT Na o i J qV Na kT e 1 qV V Cl ekT Cl Na o i J qV Cl kT e 1 Goldman Equation - Space-charge neutrality: J J J K Na Cl kT P [K ] P [Na ] P [Cl ] V ln K o Na o Cl i m q PK [K ]i PNa[Na ]i PCl [Cl ]o kT D P , P , P Permeabilities, eg. P K K K Na Cl K q : membrane width Ion Pumps - Assuming an active K+ pump, passive channels for K+ and Cl- dK[] dv JJ D ZK[] K pump Kdx K K dx dCl[] dv JD ZCl[] Cl Cldx Cl Cl dx 2kT J K [K ] [K ] pump q o i Membrane Potentials Resting Membrane Potential - Selective permeability of the membrane to ions: membrane potential - For neurons, 60 ~ 90 mV Significant ions determining the resting potential are K+, Na+, and Cl- ions: K+ ions and large immobile anions - By convention, V(out) = 0; the resting potential Vm = V(in) – V(out) = -60 mV. prevail in the intracellular space while Na+ and Cl- ions prevail in the extracellular space. Active mechanisms - Hyperpolarization: Vm < -60 mV are required to maintain the above concentration gradients across the membrane; for instance, the gradients of K+ and Na+ ions are due to the active sodium–potassium pump. - Depolarization: Vm > -60 mV • Inward electrical driving force on the permeable K+ ions, since these ions carry a positive electric charge. This electrical force opposes the •Outward chemical driving force (diffusional force) and thus limits the diffusional efflux of K+ ions. Graded Response An equilibrium is attained when the diffusional force driving K+ out of the cell is balanced by the electrical ∆Vm at the post-synaptic membrane force driving K+ into the cell. The Nernst equation gives - Due to a transformation from neurotransmitter chemical energy to electrical energy - Varies with the amount of neurotransmitter received The membrane is also slightly permeable to other ions such as Na+ and Cl- through (resting, nongated) - Sum or integration + - channel proteins in the membrane: UNa = 61 mV for Na ions and UCl = -68 mV for Cl ions. UK, UNa, UCl indicate the net driving force on the particular ion type. The Goldman–Hodgkin–Katz equation predicts the equilibrium voltage U with contributions of each ionic species. Resting Potential, Ionic Concentrations, and Channels - Resting potential: approximately -70 mV (the negative sign signifies excess negative Resting Membrane Potential charge inside the cell relative to the outside) • The factor pk quantifies the respective - Associated with ion transport and selective permeability of the membrane to ions permeability of the membrane to the k-th - Extracellular fluid: primarily Na+ and Cl- ion type; i.e., the ease with which the k-th + - ion type crosses the membrane. The typical - Cytoplasm: K and A (amino acids and proteins). ratios of permeabilities for the resting state - Ions pass through a channel. have been determined, being especially - Passive channels: always open and ion-specific (Na+, K+, Ca2+, and Cl-). applicable for the squid axon, as - Active channels: open in response to neurotransmitters and an appropriate change in membrane potential • U ~ -70 mV. The resulting electric field in the thin membrane of the cell (with the field magnitude U/d) is very high. The level of U determines the electrical force while UK, UNa, and UCl determine the respective electrochemical diffusional force. • A potential imbalance of the involved ionic concentrations in the cell, e.g., due to a slow depletion of ional gradients across the cell membrane in the course of the steady state, is prohibited by diverse active transport mechanisms in the membrane. These mechanisms maintain the ional gradients: K+ and Cl- ions are pumped back into the cell while Na+ ions back out of the cell. Equivalent Circuit Model for the Cell Membrane Equivalent Circuit Model for the Cell Membrane Equivalent Circuit Model for the Cell Membrane Neurons in Bioelectric Phenomena Introduction - Neurons - Hodgkin and Huxley model History - Galvani’s experiments with frog’s legs: action potential Neurons - nerve cells - neuroglial cells (10-50 times more, support) - cell body, dendrites (receiver), axon, and pre-synaptic terminals (transmitter) myelin sheath node of Ranvier (signal jump) -Signal velocity in the axon: 0.5 ~ 120 m/s http://stemcells.nih.gov/info/scireport/chapter8.asp GFP-tagged protein Dissociated culture in a rat hippocampal of rat hippocampal neuron neurons Université Laval, Canada Université Laval, Canada Dissociated culture of rat hippocampal neurons Université Laval, Canada Neurons • Numerous short cellular extensions, known as dendrites, which branch out in a tree-like fashion and provide a receptive area. The receptive area serves as a cellular input for graded inputs from other neurons (over neuronal synapses), from a physical stimulus (direct impact), or even from a nonneuronal receptor cell (over synapses). A membrane imbalance, known as the (electric) graded potential, is generated in this receptive area in response to any of the cellular inputs. •The cell body, known as soma, serves primarily as the metabolic center of the cell. • A single long tubular extension (from 0.1mm up to 3 m in length), known as the axon, conducts nongraded action potentials (all-or-none events). • At the end of the axon, a presynaptic terminal resides which releases a chemical transmitter in a graded manner (though in quantal steps). The transmitter release serves as a cellular output toward another neuron or a muscle cell. Types of neurons: • Sensory neurons, i.e., afferent neurons, include (or are interconnected with) sensory receptors located in the body or body’s periphery. The sensory neurons convey sensory information toward the central nervous system. Namely, sensory inputs such as light, sound, pressure, chemicals, or heat activate the corresponding receptors on the cellular level, e.g., activate gated channels for ions in the membrane of the dendrites. The resulting graded output of a receptor is converted into all-or-none action potentials which then propagate along the axon toward the neuronal synapses (as communication units with other neurons). Arriving in the central nervous system, an appropriate response is provoked, e.g., as a conscious perception or an involuntary reflex action. • Association neurons (interneurons) interconnect other neurons via synapses and ensure functional integrity of the central nervous system; These neurons comprise by far the largest class of neurons. • Motor neurons, i.e., efferent neurons, conduct action potentials from the central nervous system toward effector organs as muscle cells or glands. Namely, series of action potentials are converted into a graded release of a neurotransmitter (acetylcholine) in the neuromuscular synapses that triggers muscular contraction. Neurons • Neurons build specific (but not random) synaptic connections to other neurons, forming densely interconnected networks for functional processing, e.g., of incoming sensory information from the sensory neurons. The particular function of an embedded neuron in the network is greatly determined by its anatomical relationships to other neurons. On the input side, the neuron receives inputs either from sensory receptors (residing in the same neuron or in a receptor cell synaptically connected to this neuron, see below) or from other neurons (up to many thousands) via neuronal synapses located on dendrites and the cell body. On the output side, the axon branches out and builds collaterals (up to thousand) with the respective synapses in their terminal regions. These collaterals output a train of action potentials from the relevant neuron to numerous other neurons. In fact, the neuron is confronted with the task of decision- making based on prevailing inputs, to fire or not to fire action potentials on the output side—the very task of the nervous system. Two types of receptors cells • Primary receptors: specialized sensory neuron which exposes specific membrane regions in its bare dendrites. The free sensorial endings respond to a particular external stimulus by a corresponding graded change. The stimuli can be of thermal, mechanical, or chemical origin. Primary receptors include olfactory sensory neurons for the sense of smell. • Secondary receptors: separate nonneuronal receptor cell which is synaptically connected to an afferent sensory neuron. The receptor cell is usually highly specialized and converts the sensory stimulus (e.g., of acoustical, optical, or gustatory origin) into a graded change in its membrane potential, i.e., into its receptor potential.
Load more

Recommended publications
  • 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
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Educational Research Applications Detwiler PB., Educ Res Appl: ERCA-138 Review Article DOI: 10.29011/2575-7032/100038 Sensory Transduction: a Common Blue Print
    Educational Research Applications Detwiler PB., Educ Res Appl: ERCA-138 Review Article DOI: 10.29011/2575-7032/100038 Sensory Transduction: A Common Blue Print Peter B Detwiler Ph.D.* Department Physiology & Biophysics, School of Medicine, University of Washington, USA *Corresponding author: Peter B. Detwiler, Ph.D., Department Physiology & Biophysics, School of Medicine, University of Wash- ington, Seattle, WA 98195 USA. Tel: 1 (206) 543-0957; Email: [email protected] Citation: Detwiler PB (2017) Sensory Transduction: A Common Blue Print. Educ Res Appl: ERCA-138. DOI: 10.29011/2575- 7032/100038 Received Date: 17 October, 2017; Accepted Date: 30 October, 2017; Published Date: 07 November, 2017 Abstract Sensory receptors are transducers that convert a physical signal in the outside world into a cellular signal that can be inte- grated, transmitted, processed and interpreted by the nervous system. While the assortment of different types of sensory receptor is able to detect and selectively respond to a wide range of diverse extracellular signals they all work in basically the same way according to common blue print. They are compartmentalized input-output cells. For a specific signal to be detected it must first act on specialized membrane proteins (detector proteins) in the input or transduction region of the cell. This interaction generates a change in membrane voltage (receptor potential) by opening or closing ion channels either directly or indirectly via an enzyme cascade that controls the concentration of an intracellular second messenger (a cyclic nucleotide or calcium). The resulting electri- cal signal is communicated to the output region of the cell where it regulates Ca2+ dependent exocytosis of a chemical transmitter that carries the sensory signal to the next cell in the sensory pathway.
    [Show full text]
  • Αcgrp Is Essential for Algesic Exocytotic Mobilization of TRPV1 Channels in Peptidergic Nociceptors
    αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors Isabel Devesaa, Clotilde Ferrándiz-Huertasa, Sakthikumar Mathivanana, Christoph Wolfa, Rafael Lujánb, Jean-Pierre Changeuxc,d,1, and Antonio Ferrer-Montiela,e,1 aInstituto de Biología Molecular y Celular, Universidad Miguel Hernández, 03202 Elche, Spain; bDepartment Ciencias Médicas, Instituto de Investigación en Discapacidades Neurológicas, Facultad de Medicina, Universidad Castilla-La Mancha, 02006 Albacete, Spain; cCollège de France, 75005 Paris, France; dInstitut Pasteur, Centre National de la Recherche Scientifique, Unité de Recherche Associée, 7506 Paris, France; and eUnidad de Biofísica, Universidad del País Vasco/Euskal Herriko Unibertsitatea, Consejo Superior de Investigaciones Científicas, 48940 Leioa, Spain Contributed by Jean-Pierre Changeux, October 31, 2014 (sent for review August 12, 2014) Proalgesic sensitization of peripheral nociceptors in painful syn- LDCVs can also serve as carriers of a plethora of signaling dromes is a complex molecular process poorly understood that molecules, including ion channels and receptors that may enable involves mobilization of thermosensory receptors to the neuronal fast modulation of neuronal excitability (23). This finding raises surface. However, whether recruitment of vesicular thermoTRP the exciting hypothesis that proalgesic recruitment of TRPV1 channels is a general mechanism underlying sensitization of all channels is a mechanism occurring in peptidergic nociceptors. nociceptor types
    [Show full text]
  • Lecture 14. Insect Nerve System (II)
    Lecture 14. Insect nerve system (II) • Structures (Anatomy) – Cells – Anatomy • How NS functions – Signal transduction – Signal transmission Overview • More on neurons: ions, ion channel, ligand receptor • Signal transduction: convert various incoming sense signals into electric signals – Chemotransduction: chemical signals (smell, taste) – Phototransduction: visual cues (see) – Mechanotransduction: mechanical signals (hear, feel touching) • Signal transmission – Axon transmission – Synaptic transmission Neuron: ions and resting potential • Asymmetrical distribution of ions: more Na+ (>10- fold), Ca2+ (10,000- fold), and Cl- but less K+ (<20-fold) outside the cell. EXCEPTION: some intracellular membrane-bounded compartments (ER) may have high Ca2+ • Two ion pumps (Na+/K+ ATPase, Ca2+ ATPase) and the presence of “leaky” K+ channels (red arrow): Na+/K+ ATPase pumps 3 Na+ out and 2K+ into the cell at the expense of 1 ATP; Ca2+ ATPase pump Ca2+ out the cell. http://highered.mcgraw-hill.com/olc/dl/120107/bio_a.swf • A resting potential of about -70 millivolts (mv) for neurons: an electrical charge across the plasma membrane, with the interior of the cell negative with respect to the exterior. • Cells are polarized Neuron: ion channels • Ion Channels are pore-forming transmembrane proteins. Channels are closed at the Na+, K+, Ca2+ , Cl- resting state • Stimulus can open ion channels ++++++++++++++++++++++++ • Ions may flow in or out in down- hill directions when their corresponding channels are open _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ • Cross-membrane movements of Na+, K+, Ca2+, Cl- ions lead to potential changes across membrane---electrical signals Ion channels: gating mechanisms • Mechanically-gated channels: open or close in response to mechanical forces that arise from local stretching or compression of the membrane around them • Voltage-gated ion channels: open in response to the transmembrane potential changes.
    [Show full text]
  • The Transformations of Sound Stimuli Into Electrical Signals
    The transformation of sound stimuli into electrical signals 2 Robert Fettiplace 1 Introduction Our sense of hearing depends on the correct performance of about 15 000 hair cells in each cochlea that serve as an interface between the mechanical vibrations of speech, music and other sounds and the electrical signals of the brain. Hair cells can detect vibrations of atomic dimensions down to 0.2 nm, and can respond more than 20 000 times a second. These cells cannot regenerate, so their atrophy in old age or destruction by loud sounds or drugs like streptomycin causes permanent deafness. Loss of sensation is often restricted to higher frequencies, and is linked to degeneration of hair cells near one end of the cochlea. This chapter explains how acoustic stimuli are detected by the hair cells and converted into a stream of electrical impulses that are relayed to the brain. It also describes the mechanisms by which each cell is affiliated with certain input frequencies. 2 Hair cells and their mode of stimulation Hair cells are the sensory receptors for all components of the inner ear, including the organ of hearing, the cochlea, and those of balance – three semicircular canals, a saccule and utricle (see Chapter 7, The vestibular system). In each of these the hair cells are tightly anchored to non-sensory supporting cells in an epithelial sheet. In the cochlea, this sheet of cells, known as the organ of Corti, rests on a freely moveable basilar membrane (Figure 1a overleaf). The mechanically sensitive hair bundles project above the epithelial surface and the majority contact a gelatinous flap known as the tectorial membrane.
    [Show full text]
  • 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; [email protected] (F.A.-C.); [email protected] (D.A.-S.); [email protected] (M.d.C.A.); [email protected] (C.B.); [email protected] (J.G.) 2 Department of Medical Neurobiology, Institute for Medical Research Israel—Canada, Hadassah School of Medicine, The Hebrew University, Jerusalem 91123, Israel; [email protected] (N.E.); [email protected] (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: [email protected] † 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.
    [Show full text]
  • Biophysics and Modeling of Mechanotransduction in Neurons: a Review
    mathematics Review Biophysics and Modeling of Mechanotransduction in Neurons: A Review Martina Nicoletti 1,2,† , Letizia Chiodo 1,† and Alessandro Loppini 1,∗,† 1 Nonlinear Physics and Mathematical Models Research Unit, Engineering Department, Campus Bio-Medico University of Rome, Via Á. del Portillo 21, 00128 Rome, Italy; [email protected] (M.N.); [email protected] (L.C.) 2 Center for Life Nanoscience CLNS@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy * Correspondence: [email protected]; Tel.: +39-06225419660 † These authors contributed equally to this work. Abstract: Mechanosensing is a key feature through which organisms can receive inputs from the environment and convert them into specific functional and behavioral outputs. Mechanosensa- tion occurs in many cells and tissues, regulating a plethora of molecular processes based on the distribution of forces and stresses both at the cell membrane and at the intracellular organelles levels, through complex interactions between cells’ microstructures, cytoskeleton, and extracellular matrix. Although several primary and secondary mechanisms have been shown to contribute to mechanosensation, a fundamental pathway in simple organisms and mammals involves the presence of specialized sensory neurons and the presence of different types of mechanosensitive ion channels on the neuronal cell membrane. In this contribution, we present a review of the main ion channels which have been proven to be significantly involved in mechanotransduction in neurons. Further, we discuss recent studies focused on the biological mechanisms and modeling of mechanosensitive ion channels’ gating, and on mechanotransduction modeling at different scales and levels of details. Keywords: mechanosensing; mechanotransduction; ion channels; neurons; modeling; atomistic Citation: Nicoletti, M.; Chiodo, L.; modeling; molecular dynamics; multiscale; biomechanics; mechanobiology Loppini, A.
    [Show full text]
  • Action Potential Propagation
    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: [email protected] 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.
    [Show full text]
  • Lecture 4 Introduction Introduction Receptor Physiology
    The Cyprus International Institute for the Environment and Public Health In collaboration with the Harvard School of Public Health Introduction • Peripheral Nervous System Lecture 4 • Afferent Division • Sends information from the PNS to the CNS • Efferent Division The Peripheral Nervous System • Send information from the CNS to the PNS • Afferent Division (181-240) • Visceral afferents (subconscious input) • Pressure, O2, temperature, etc. • Sensory afferents (conscious input) Excluded: adaptation of pacinian corpuscle (185), labeled lines • Somatic sensation (186), acuity (186-187), phototransduction (200-203), on- off- center • Somesthetic sensation from skin • Proprioception from muscle joints, skin and ganglion cells (205) inner ear • Special senses • Vision, hearing, taste and smell • Efferent Division • Autonomic Nervous System Constantinos Pitris, MD, PhD • Cardiac muscle, smooth muscle, most exocrine glands, some endocrine glands, Assistant Professor, University of Cyprus adipose tissue [email protected] • Somatic Nervous system http://www.eng.ucy.ac.cy/cpitris/courses/CIIPhys/ • Skeletal muscle 2 Introduction Receptor Physiology • Sensation ≠ Perception • Receptors • Detect stimulus (detectable change) from different modalities (energy forms) • Perception • e.g. light, heat, sound, pressure, chemical changes • Our understanding (conscious • Adequate stimulus = the stimulus to which the receptor is most sensitive interpretation) of the physical world • Convert forms of energy into electrical signals (action potentials) • An interpretation
    [Show full text]