Lect. 2: Nervous System I - Resting Potential
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Chapter 1 Zoom in On… Patch Configurations in the Jargon of Electrophysiologists, a Patch Is a Piece of Neuronal Membrane
CELLULAR NEUROPHYSIOLOGY CONSTANCE HAMMOND Chapter 1 Zoom in on… Patch configurations In the jargon of electrophysiologists, a patch is a piece of neuronal membrane. Researchers invented a technique known as a patch-clamp, which records the current through a single ion channel, some ion channels or through all open ion channels in the neuron membrane. To obtain these recordings, researchers use different patch configurations. We'll explain here only the three configurations used in the course: the cell-attached configuration, the whole-cell configuration, and the "outside-out" excised patch configuration. According to the type of recording to perform, a particular type of configuration will be chosen: 1. to record a unitary current: cell-attached or outside-out configuration; 2. to record a total current: whole-cell configuration; 3. to record changes in membrane potential (action potentials or postsynaptic potentials): whole-cell configuration. The cell-attached configuration (attached to the pipette - Figure a) First, the pipette is filled with an extracellular fluid. Positive pressure is applied in the electrode by means of a syringe connected to the electrode, so that the intrapipette fluid tends to leave the pipette. The electrode is then brought near to the soma of a neuron. When the electrode touches the membrane, the positive pressure is withdrawn to draw the membrane toward the mouth of the pipette. We wait without moving the pipette; a seal is made between the walls of the pipette and the soma membrane. This seal strength can be measured by applying a low level of amplitude current in the pipette. Since V = RI, one can measure the resistance of the seal. -
A Thermodynamic Description for Physiological Transmembrane Transport
A thermodynamic description for physiological transmembrane transport Marco Arieli Herrera-Valdez 1 1 Facultad de Ciencias, Universidad Nacional Autónoma de México marcoh@ciencias:unam:mx April 16, 2018 Abstract Physiological mechanisms for passive and active transmembrane transport have been theoretically described using many different approaches. A generic formulation for both passive and active transmem- brane transport, is derived from basic thermodynamical principles taking into account macroscopic forward and backward molecular fluxes, relative to a source compartment, respectively. Electrogenic fluxes also depend on the transmembrane potential and can be readily converted into currents. Interestingly, the conductance-based formulation for current is the linear approximation of the generic formulation for current, around the reversal potential. Also, other known formulas for current based on electrodiffusion turn out to be particular examples of the generic formulation. The applicability of the generic formulations is illustrated with models of transmembrane potential dynamics for cardiocytes and neurons. The generic formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport. 1 Introduction One of the most important physiological mechanisms underlying communication within and between cells is the transport of molecules across membranes. Molecules can cross membranes either passively (Stein and Litman, 2014), or via active transport (Bennett, 1956). Passive transmembrane transport occurs through pores that may be spontaneously formed within the lipid bilayer (Blicher and Heimburg, 2013), or within transmembrane proteins called channels (Hille, 1992; Stein and Litman, 2014) that may be selective for particular ion types (Almers and McCleskey, 1984; Doyle et al., 1998; Favre et al., 1996). -
Nernst Potentials and Membrane Potential Changes
UNDERSTANDING MEMBRANE POTENTIAL CHANGES IN TERMS OF NERNST POTENTIALS: For seeing how a change in conductance to ions affects the membrane potential, follow these steps: 1. Make a graph with membrane potential on the vertical axis (-100 to +55) and time on the horizontal axis. 2. Draw dashed lines indicating the standard Nernst potential (equilibrium potential) for each ion: Na+ = +55 mV, K+ = -90mV, Cl- = -65 mV. 3. Draw lines below the horizontal axis showing the increased conductance to individual ions. 4. Start plotting the membrane potential on the left. Most graphs will start at resting potential (-70 mV) 5. When current injection (Stim) is present, move the membrane potential upward to Firing threshold. 6. For the time during which membrane conductance to a particular ion increases, move the membrane potential toward the Nernst potential for that ion. 7. During the time when conductance to a particular ion decreases, move the membrane potential away from the Nernst potential of that ion, toward a position which averages the conductances of the other ions. 8. When conductances return to their original value, membrane potential will go to its starting value. +55mV ACTION POTENTIAL SYNAPTIC POTENTIALS 0mV Membrane potential Firing threshold Firing threshold -65mV -90mV Time Time Na+ K+ Conductances Stim CHANGES IN MEMBRANE POTENTIAL ALLOW NEURONS TO COMMUNICATE The membrane potential of a neuron can be measured with an intracellular electrode. This 1 provides a measurement of the voltage difference between the inside of the cell and the outside. When there is no external input, the membrane potential will usually remain at a value called the resting potential. -
Effect of Hyperkalemia on Membrane Potential: Depolarization
❖ CASE 3 A 6-year-old boy is brought to the family physician after his parents noticed that he had difficulty moving his arms and legs after a soccer game. About 10 minutes after leaving the field, the boy became so weak that he could not stand for about 30 minutes. Questioning revealed that he had complained of weakness after eating bananas, had frequent muscle spasms, and occasionally had myotonia, which was expressed as difficulty in releasing his grip or diffi- culty opening his eyes after squinting into the sun. After a thorough physical examination, the boy was diagnosed with hyperkalemic periodic paralysis. The family was advised to feed the boy carbohydrate-rich, low-potassium foods, give him glucose-containing drinks during attacks, and have him avoid strenuous exercise and fasting. ◆ What is the effect of hyperkalemia on cell membrane potential? ◆ What is responsible for the repolarizing phase of an action potential? ◆ What is the effect of prolonged depolarization on the skeletal muscle Na+ channel? 32 CASE FILES: PHYSIOLOGY ANSWERS TO CASE 3: ACTION POTENTIAL Summary: A 6-year-old boy who experiences profound weakness after exer- cise is diagnosed with hyperkalemic periodic paralysis. ◆ Effect of hyperkalemia on membrane potential: Depolarization. ◆ Repolarization mechanisms: Activation of voltage-gated K+ conductance and inactivation of Na+ conductance. ◆ Effect of prolonged depolarization: Inactivation of Na+ channels. CLINICAL CORRELATION Hyperkalemic periodic paralysis (HyperPP) is a dominant inherited trait caused by a mutation in the α subunit of the skeletal muscle Na+ channel. It occurs in approximately 1 in 100,000 people and is more common and more severe in males. -
Electrical Activity of the Heart: Action Potential, Automaticity, and Conduction 1 & 2 Clive M
Electrical Activity of the Heart: Action Potential, Automaticity, and Conduction 1 & 2 Clive M. Baumgarten, Ph.D. OBJECTIVES: 1. Describe the basic characteristics of cardiac electrical activity and the spread of the action potential through the heart 2. Compare the characteristics of action potentials in different parts of the heart 3. Describe how serum K modulates resting potential 4. Describe the ionic basis for the cardiac action potential and changes in ion currents during each phase of the action potential 5. Identify differences in electrical activity across the tissues of the heart 6. Describe the basis for normal automaticity 7. Describe the basis for excitability 8. Describe the basis for conduction of the cardiac action potential 9. Describe how the responsiveness relationship and the Na+ channel cycle modulate cardiac electrical activity I. BASIC ELECTROPHYSIOLOGIC CHARACTERISTICS OF CARDIAC MUSCLE A. Electrical activity is myogenic, i.e., it originates in the heart. The heart is an electrical syncitium (i.e., behaves as if one cell). The action potential spreads from cell-to-cell initiating contraction. Cardiac electrical activity is modulated by the autonomic nervous system. B. Cardiac cells are electrically coupled by low resistance conducting pathways gap junctions located at the intercalated disc, at the ends of cells, and at nexus, points of side-to-side contact. The low resistance pathways (wide channels) are formed by connexins. Connexins permit the flow of current and the spread of the action potential from cell-to-cell. C. Action potentials are much longer in duration in cardiac muscle (up to 400 msec) than in nerve or skeletal muscle (~5 msec). -
9.01 Introduction to Neuroscience Fall 2007
MIT OpenCourseWare http://ocw.mit.edu 9.01 Introduction to Neuroscience Fall 2007 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. 9.01 Recitation (R02) RECITATION #2: Tuesday, September 18th Review of Lectures: 3, 4 Reading: Chapters 3, 4 or Neuroscience: Exploring the Brain (3rd edition) Outline of Recitation: I. Previous Recitation: a. Questions on practice exam questions from last recitation? II. Review of Material: a. Exploiting Axoplasmic Transport b. Types of Glia c. THE RESTING MEMBRANE POTENTIAL d. THE ACTION POTENTIAL III. Practice Exam Questions IV. Questions on Pset? Exploiting Axoplasmic Transport: Maps connections of the brain Rates of transport: - slow: - fast: Examples: Uses anterograde transport: - Uses retrograde transport: - - - Types of Glia: - Microglia: - Astrocytes: - Myelinating Glia: 1 THE RESTING MEMBRANE POTENTIAL: The Cast of Chemicals: The Movement of Ions: Influences by two factors: (1) Diffusion: (2) Electricity: Ohm’s Law: I = gV Ionic Equilibrium Potentials (EION): + Example: ENs * diffusional and electrical forces are equal 2 Nernst Equation: EION = 2.303 RT/zF log [ion]0/[ion]i Calculates equilibrium potential for a SINGLE ion. Inside Outside EION (at 37°C) + [K ] + [Na ] 2+ [Ca ] [Cl ] *Pumps maintain concentration gradients (ex. sodiumpotassium pump; calcium pump) Resting Membrane Potential (VM at rest): Measured resting membrane potential: 65 mV Goldman Equation: + + + + VM = 61.54 mV log (PK[K ]o + PNa[Na ]o)/ (PK[K ]I + PNa[Na ]i) + + Calculates membrane potential when permeable to both Na and K . Remember: at REST, gK >>> gNa therefore, VM is closer to EK THE ACTION POTENTIAL (Nerve Impulse): Phases of an Action Potential: Vm (mV) ENa 0 EK Time 3 Conductance of Ion Channels during AP: Remember: Changes in conductance, or permeability of the membrane to a specific ion, changes the membrane potential. -
The Action Potential
See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/6316219 The action potential ARTICLE in PRACTICAL NEUROLOGY · JULY 2007 Source: PubMed CITATIONS READS 16 64 2 AUTHORS, INCLUDING: Mark W Barnett The University of Edinburgh 21 PUBLICATIONS 661 CITATIONS SEE PROFILE Available from: Mark W Barnett Retrieved on: 24 October 2015 192 Practical Neurology HOW TO UNDERSTAND IT Pract Neurol 2007; 7: 192–197 The action potential Mark W Barnett, Philip M Larkman t is over 60 years since Hodgkin and called ion channels that form the permeation Huxley1 made the first direct recording of pathways across the neuronal membrane. the electrical changes across the neuro- Although the first electrophysiological nal membrane that mediate the action recordings from individual ion channels were I 2 potential. Using an electrode placed inside a not made until the mid 1970s, Hodgkin and squid giant axon they were able to measure a Huxley predicted many of the properties now transmembrane potential of around 260 mV known to be key components of their inside relative to outside, under resting function: ion selectivity, the electrical basis conditions (this is called the resting mem- of voltage-sensitivity and, importantly, a brane potential). The action potential is a mechanism for quickly closing down the transient (,1 millisecond) reversal in the permeability pathways to ensure that the polarity of this transmembrane potential action potential only moves along the axon in which then moves from its point -
Nernst Equation - Wikipedia 1 of 10
Nernst equation - Wikipedia 1 of 10 Nernst equation In electrochemistry, the Nernst equation is an equation that relates the reduction potential of an electrochemical reaction (half-cell or full cell reaction) to the standard electrode potential, temperature, and activities (often approximated by concentrations) of the chemical species undergoing reduction and oxidation. It was named after Walther Nernst, a German physical chemist who formulated the equation.[1][2] Contents Expression Nernst potential Derivation Using Boltzmann factor Using thermodynamics (chemical potential) Relation to equilibrium Limitations Time dependence of the potential Significance to related scientific domains See also References External links Expression A quantitative relationship between cell potential and concentration of the ions Ox + z e− → Red standard thermodynamics says that the actual free energy change ΔG is related to the free o energy change under standard state ΔG by the relationship: where Qr is the reaction quotient. The cell potential E associated with the electrochemical reaction is defined as the decrease in Gibbs free energy per coulomb of charge transferred, which leads to the relationship . The constant F (the Faraday constant) is a unit conversion factor F = NAq, where NA is Avogadro's number and q is the fundamental https://en.wikipedia.org/wiki/Nernst_equation Nernst equation - Wikipedia 2 of 10 electron charge. This immediately leads to the Nernst equation, which for an electrochemical half-cell is . For a complete electrochemical reaction -
Membrane Potentials As Signals
Membrane Potentials as Signals The membrane potential allows a cell to function as a battery, providing electrical power to activities within the cell and between cells. KEY POINTS A membrane potential is the difference in electrical potential between the interior and the exterior of a biological cell. In electrically excitable cells, changes in membrane potential are used for transmitting signals within the cell. The opening and closing of ion channels can induce changes from the resting potential. Depolarization is when the interior voltage becomes more positive and hyperpolarization when it becomes more negative. TERMS Graded potentials Graded potentials vary in size and arise from the summation of the individual actions of ligand- gated ion channel proteins, and decrease over time and space. Depolarization Depolarization is a change in a cell's membrane potential, making it more positive, or less negative, and may result in generation of an action potential. Action potential A short term change in the electrical potential that travels along a cell such as a nerve or muscle fiber. EXAMPLE In neurons, a sufficiently large depolarization can evoke an action potential in which the membrane potential changes rapidly. Give us feedback on this content: Membrane potential (also transmembrane potential or membrane voltage) is the difference in electrical potential between the interior and the exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it. The membrane serves as both an insulator and a diffusion barrier to the movement of ions. -
1 Probing the Membrane Potential of Living Cells by Dielectric
Probing the membrane potential of living cells by dielectric spectroscopy Corina Bot and Camelia Prodan Dept. of Physics, New Jersey Inst. of Techn, Newark, NJ Abstract. In this paper we demonstrate a quantitative way to measure the membrane potential of live cells by dielectric spectroscopy. We also show that the values of the membrane potential obtained using our technique are in good agreement with those obtained using traditional methods-voltage sensitive dyes. The membrane potential is determined by fitting the experimental dielectric dispersion curves with the dispersion curves obtain from a theoretical model. Variations in the membrane potential were induced by modifying the concentration of potassium chloride in the solution of the cell suspension in the presence of valinomycin. For exemplification of the method, E. coli were chosen for our experiments. Introduction The resting membrane potential is one of the most important living cell parameters. By monitoring a cell’s membrane potential, one can get important information about its state. Changes in the membrane potential have been linked to different diseases, including Parkinson’s, epilepsy and Bartter’s syndrome [1]. A decrease in the plasma membrane potential has been seen in tumor cells with increased expression of multi-drug resistance (MDR) protein, also known as P-glycoprotein [2]. It was also shown that the membrane potential plays a critical role in the antibiotic uptake by cells and in bactericidal action [3]. Thus measuring or monitoring the membrane potential is of great importance. The existing “gold” or standard methods to measure or monitor the membrane potential are patch clamping and voltage sensitive dyes. -
Chapter 7 Transport of Ions in Solution and Across Membranes
Chapter 7 Transport of ions in solution and across membranes 7-1. Introduction 7-2. Ionic fluxes in solutions 7-2.1. Fluxes due to an electrical field in a solution 7-2.2. Flux due to an electrochemical potential gradient 7-3. Transmembrane potentials 7-3.1. The Nernst potential, the single ion case where the flux is zero 7-3.2. Current-voltage relationships of ionic channels 7-3.3. The constant field approximation 7-3.4. The case of a neutral particle 7-4. The resting transmembrane potential, ER 7-4.1. Goldman-Hodgkin-Katz expression for the resting potential 7-4.2. Gibbs-Donnan equilibrium and the Donnan potential 7-4.3. Electrodiffusion 7-5. Patch clamp studies of single-channel kinetics 7-6. The action potential in excitable cells 7-6.1. Neuronal currents 7-6.2. The Hodgkin-Huxley nerve action potential 7-6.3. The voltage clamp methods for measuring transmembrane currents 7-6.4. Functional behavior of the nerve axon action potential 7-6.5. Cardiac and other action potentials 7-7. Propagation of the action potential 7-7.1. The cable equations 7-7.2. The velocity of propagation 7-8. Maintaining ionic balance: Pumps and exchangers 7-9. Volume changes with ionic fluxes 7-10. Summary 7-11. Further reading 7-12. Problems 7-13. References 7-13.1. References from previous reference list not appearing in current text or references This chapter lacks the following: Tables and programs. Completion of later parts on the pumps. Complete cross referencing. Improvements in Figures. -
Resting Potential and Chloride Channels
Neurobiology – resting potential and chloride channels Rudolf Cardinal, 4 Feb 99 • Ionic concentrations are determined and maintained by the activity of ionic pumps, including the Na+–K+ ATPase (pumping 3 + + + – + – + + Na out and 2 K in), the K /Cl cotransporter (using the K gradient to extrude Cl ), the active Ca pump (extruding Ca and us- ing ATP) and the Na+/Ca2+ exchanger (using the Na+ gradient to extrude Ca+, 3 Na+ in to 1 Ca2+ out). Action potentials involve the transfer of too few ions to affect the ionic concentration significantly (a drop in the ocean) so we can ignore their effects. • Actual ionic concentrations in mammalian neurons: Ion Internal concentration External concentration Valence (z) Equilibrium potential Na+ 15 mM 150 mM +1 +62 mV K+ 150 mM 5.5 mM +1 –89 mV Cl– 9 mM 125 mM –1 –71 mV Ca2+ 10–4 mM 1 mM +2 +124 mV • Equilibrium potential for each ion is determined solely by the concentration gradient and valence, by the Nernst equation: E = –1 –1 (RT/zF) ln(concout/concin). R is the gas constant (8.314 J deg mol ); T is the absolute temperature (37°C = 310 K); z is the va- lence for the ion; F is Faraday’s constant (96500 C mol–1); E is in volts. • Remember that an ion will not flow across a membrane if the potential gradient equals that ion’s equilibrium potential (by defi- nition). • The resting potential is determined by the equilibrium potentials for every ion to which the membrane is permeable, weighted + + – + + by the permeability (p), via th Goldman equation: E = (RT/F) ln[ (pK[K ]out + pNa[Na ]out + pCl[Cl ]in) / (pK[K ]in + pNa[Na ]in + – pCl[Cl ]out)].