3/20/2017 Organismic Biology Bio 207 Lecture4 Internal communication: neurons, resting membrane potentials, action potentials; voltage-gated channels Dr. Simchon Remember Next week is your 1st exam Will cover lectures 1-3 and Tutorial 1 The labs are not covered Exam: multiple choice, multiple answers, calculations, graphs, essay 1 3/20/2017 Remember salt balance Hyper-osmoregulator Hypo-osmoregulator Hyper-osmoregulator Hypo-osmoregulator 2 3/20/2017 Osmotic Hyper-regulation 100 mOsm Passive diffusion of Solutes Passive diffusion of Solutes ECF (organism) 300 mOsm Active uptake of ECF (organism) 900 mOsm Active uptake of Solutes Solutes Which organism will spend more energy? Mode of osmo-regulation Hyper-osmoregulator C and B ECF conc (mOsm) C D B B A A = line of identity Hypo-osmoregulator D and B Environment conc (mOsm) Which organism will spend more energy at external 100mOsm? Which organism will spend more energy at external 900mOsm? 3 3/20/2017 Role of ADH and ANP ANP = Atrial Natriuretic (sodium = Na) hormone = Diuretic hormone ADH = Antidiuretic hormone Renal Regulation The ability to concentrate urine by reabsorption of filtered water, will save us from having to drink large amount of water and to have frequent trips to the bathroom . The ability to concentrate urine depends on: (a) countercurrent system. (b) Antidiuretic Hormone (ADH) level (c) ANP level and sodium reabsorption 4 3/20/2017 Medium term adaptation to lower its water output Important for exam Increase ADH concentrate urine (increase reabsorption of water) How can you tell that urine is concentrated? By measuring urine/plasma osmolarity ratio Urine Osm/Plasma Osm = 1 Expected ADH level Urine Osm/Plasma Osm = 0.5 Expected ADH level Pl. Osm = 300; U Osm = 300 mOsm Pl. Osm = 300; U Osm = 150 mOsm Urine Osm/Plasma Osm = 4 Expected ADH level Pl. Osm = 300; U Osm = 1200 What is the long term adaptation to concentrate urine? Figure 26.7 The interpretive significance of the osmotic U/P ratio 5 3/20/2017 Figure 15.14 The action of an antidiuretic hormone 6 3/20/2017 The Effects of ADH 7 3/20/2017 New stuff 2nd exam Nervous system Agenda • Intro to communication – Nervous system overview – Resting Membrane Potential – Action Potentials – Action Potential Conduction – The Synapse – Post-synaptic cell responses Coordination of organismic function: the thread • Integrating the function of tens of trillions of cells organized into hundreds of tissues and many organ systems: the evolution of multicellular organisms has depended upon the ability of cells to communicate with each other across great distances • responding rapidly and in a sustained way over long periods of time • control systems are necessary 8 3/20/2017 Two types of coordination pathways • Neuronal: rapid signaling specifically addressable (individual cells and locations) example: fine movement control; sensory input • Hormonal: mid- to long-term signaling widely broadcast with all receptive cells responding examples: cellular metabolism; organ function Two types of system-level communication 9 3/20/2017 The Nervous System Chapter 48 Topics to be covered 1. Organization of the Nervous System 2. How does information carried out and transported in nerve? 3. How does information submitted from one nerve to another? Organization of the Nervous System • Central nervous system (CNS) – Brain and spinal cord – Integration and command center • Peripheral nervous system (PNS) – Carries messages to and from the spinal cord and brain. That portion of the nervous system that is outside the brain and spinal cord. 10 3/20/2017 Organization of the Nervous System Organization of the Nervous System Central Nervous System Peripheral Nervous System afferent efferent 11 3/20/2017 Organization of the Nervous System Central Nervous System (CNS) Enteric Nervous System Peripheral Nervous System (PNS) Efferent division of PNS Sensory division of PNS Sensory receptors Efferent division of PNS Autonomic involuntary Sympathetic Somatic voluntary Parasympathetic Heart, lung, etc Skeletal muscles Afferent Pathway = Input to brain Sensory - 5 senses: o Sight o Smell o Taste o Touch o Hearing 12 3/20/2017 How does information carried out and transported in nerve? Electrical impulses = Action Potential Very fast How does neural information travel? 13 3/20/2017 What is the signal nerves use? How can cells act like wires? • electrical impulses traveling along the nerve cell from end to end: dendrites to axon terminus • Neurotransmission: chemical transmission links nerve cells and the cells with which they communicate Dendrites Cell body Presynaptic terminal Source: Animal Physiology, 3rd Edition by Hill, Wyse and Anderson, Sinauer Press What electrical properties of cells permit information transfer in nerves? • all cells have electric properties and polarity • Most cells are passive and do not conduct charge • neuronal cells are active and do conduct a charge down their length • to understand both active and passive cell potentials we must understand the cell membrane 14 3/20/2017 Electricity Basics • Electric current (I): net movement of charge – measured in amperes or milliamperes – A or mA (ions in cells; electrons in wires) • Voltage: separation of charge/ electrical potential difference (V) – measured in volts or millivolts - V or mV • Resistance (R): element that impedes current flow – measured in Ohms - Ω • Capacitance (C): storage of charge – measured in farads - F Ohms Law ∆V I = ----R I = current V = voltage difference R = resistance 15 3/20/2017 All cells have an electric potential difference from inside to outside: Membrane potential •difference in charge between the inside and outside of the cell membrane •usually negative inside relative to outside •polarity is determined by the distribution of ions across the cell membrane Transmembrane charge 16 3/20/2017 Membrane Potential (Vm) • Membrane potential (Vm) is the transmembrane potential: the electrical charge difference across the membrane that results from the separation of charges across the cell membrane. It has a value and a sign. • Sign refers to the intracellular charge. Example: if Vm = -70 mV indicates that the inside of cell is 70 mV more negative than the outside of cell. • Determinants: Permeability to specific ions (R) and ionic concentrations (Cin – Cout) What do we find if we measure cellular and extracellular ion concentrations? 17 3/20/2017 Some typical extracellular and intracellular fluid values Extracell (mEq/L) Intracellular (mEq/L) 2 74 Sodium - Na+ 145 15 Potassium - K+ 5 150 Calcium - Ca++ 1 0.0001 Magnesium - Mg++ 3 26 Chloride - Cl- 108 10 Bicarbonate - HCO3- 27 10 PO4- 2 113 non-electrolyte 10 10 Protein Why are there concentration differences inside to outside? • Active transport of some ions - Na+-K+-ATPase • Varying passive diffusion of others based on individual permeability 18 3/20/2017 Electrogenic pumps • Do not pump equal charge in and out • Na+-K+=ATPase pumps Na+-K+ in a 3:2 ration, thus producing a net current, and is electrogenic • This functions to offset passive leaking of ions across the membrane, and to directly impact Vm • What would be the Na+-K+ pumping ratio of an electroneutral pump? Only a few ions are needed to create polarity • 110,000 anions and 110,000 cations on each side of membrane • Only 6 pairs of ions create a 90mV membrane potential 19 3/20/2017 Passive Transport of Particles A. Particles without charge B. Particles with charge Simple diffusion of particles without charge Compartment 1 Compartment 2 A A C1 > C2 Concentrations C1 > C2 2 1 Substance A will move from to _______ The Driving force is: Concentration gradient Diffusion Fick law = K (C1 - C2) 20 3/20/2017 Simple diffusion of particles without charge Compartment 1 Compartment 2 A C1 > Concentrations C1 > C2 Substance A will move from The Driving force is: A C2 to _______ Electrical effects in simple diffusion • Positive charges are attracted to negative charges • Similar charges repel each other • A large electrical difference may cause a solute to move in such a direction so as to increase the concentration difference. 21 3/20/2017 Electrical effects in simple diffusion Compartment 1 - + Compartment 2 A+ A+ C1 = Concentrations C1 = C2 Substance A will move from The Driving force is: C2 (same) to _______ Electrical effects in simple diffusion Compartment 1 - + Compartment 2 A+ A+ C1 > C2 Concentrations C1 > C2 Substance A will move from The Driving force is: to _______ Fick diffusion equation 22 3/20/2017 Nernst Equilibrum Movement will stop when : ____________________________ Nernst Equilibrium: Vm = Ei Vm = electrical potential of membrane Ei = chemical potential of membrane [Nernst = f(C1-C2)] Electrochemical gradient Ions and semi-permeable membranes Equilibrium both sides Concentrations of solutes equal and ion charge balanced If an ion is too large to cross the membrane, other electrical charges will move to maintain a balance in charge and conc. 23 3/20/2017 Ions and semi-permeable membranes Equilibrium both sides Concentrations of solutes equal and ion charge balanced If an ion is too large to cross the membrane, other electrical charges will move to maintain a balance in charge and conc. Electrical effects in simple diffusion Outside cell Inside cell Na+ K+ 24 3/20/2017 If only K+ is permeable Outside cell Inside cell K+ If only Na+ is permeable Outside cell Inside cell Na+ 25 3/20/2017 THE NERNST EQUATION Since both the concentration gradient and the transmembrane potential affect the movement of ions, we must be able determine the relative magnitudes of these two forces. The Nernst equation does this. Using the equation, a Nernst potential can be calculated for every ion in the cell. What does that tell you? If you force the cell to be at the Nernst potential for a certain ion, then that ion will not cross the membrane, even if a channel for it is open, because the electrical potential will exactly balance the concentration difference. RT C1 Em = ---------ln-------zF C2 -1 -1 R = universal gas constant (8.314 J mol K ), T = absolute temperature (in K), z =valence of ion (i.e. Cl- = -1), F = Faraday's constant (96485 C). Resting membrane potentials depend upon selective permeability to ions and active ion pumping 26 3/20/2017 Balancing concentration and charge • Both the concentration gradient (Cin - Cout) and the transmembrane potential (Vm) affect the movement of ions so we must be able determine the relative magnitudes of these two forces • The Nernst equation does this. Using the equation, a Nernst potential can be calculated for every ion in the cell. • What does that tell you? If you force the cell to be at the Nernst potential for a certain ion, then that ion will not cross the membrane, even if a channel for it is open, because the electrical potential will exactly balance the concentration difference. Nernst equation Membrane potential due to the distribution of one ion if it were fully permeable RT Cout E = ----- ln ----zF Cin E is membrane potential (electromotive force) R is the gas constant (8.314 J mol-1 K-1), T is absolute temperature (in K) z is the valence of the ion (i.e. Cl- = -1), F is Faraday’s constant – charge per mole of ions (96,485 C). C is the ionic concentration inside and outside 27 3/20/2017 Simplified Nernst equation (at 37o C) 61 Cout E = ---- log10 ----z Cin E is membrane potential in mV C is the ionic concentration inside and out z is the valence of the ion Ei is the equilibrium potential for a particular ion • The value of the membrane potential at which the ion is at electrochemical equilibrium and there is no net ionic movement across the membrane • Meaning: the electrical force on the ion is exactly balanced by the chemical concentration (force) • This condition does not exist for any ion in the body except for transiently 28 3/20/2017 Nernst Equilibrium At Nernst equilibrium: Vm = Ei • • Vm = electrical potential difference across membrane Ei = chemical potential across membrane for a given ion [Nernst = f(C1-C2)] At 37oC At 25oC Em = 61/z log10 Cout/Cin Em = 58/z log10 Cout/Cin C1 - C2 is the concentration gradient (assuming it is across the plasma membrane – distance is a parameter for a gradient) Complete the Table Ion Concentration Inside Cell outside cell K+ Na+ Cl- 150 mEq/L 15 mEq/L 10 mEq/L At 37ºC: 60 log10 Cout/Cin Nernst Equilibrium Magnitude 4 mEq/L 145 mEq/L 108 mEq/L At 37 º C: 1. What will be the electrical charge across membrane if only K+ is permeable? What is the polarity? 2. What will be the electrical charge across membrane if only Na+ is permeable? What is the polarity? 3. What will be the electrical charge across membrane if only Cl- is permeable? What is the polarity 29 3/20/2017 But more than one ion is responsible for Vm • Vm is largely determined by K+ concentrations inside and outside because the cell membrane is most permeable to K+ • However, other ions, particularly Na+ and Cl-, are also important for Vm • Other ions can be ignored because of either very low membrane permeabilities (ie. HCO3- ) or very low concentrations (H+) • The Goldman equation combines the contributions of K+, Na+ and Cl- to derive Vm Goldman Equation (GHK) RT Pk [K+]o + PNa [Na+]o + PCl [Cl-]i Vm = ---- log ----------------------------------------F Pk [K+]i + PNa [Na+]i + PCl [Cl-]o Pk , PNa and PCl are the relative permeabilities for K+ , Na+ and Cl- 30 3/20/2017 Actual Vm may be anywhere between these: If the membrane were permeable only to Na+ : ENa = 58 log (145/15) = +59 mV Membrane potential (mV) +59 Pk [K+]o + PNa [Na+]o Vm = 58 log ---------------------------Pk [K+]i + PNa [Na+]i If the membrane were permeable only to K+ : Ek = 58 log (4/150) = -94 mV ENa 0 -65 Em (resting) -94 EK Extreme cases For the squid giant axon: • 25o C • Ignoring Cl• [K+]o = 20 mM [K+]i = 400 mM • [Na+]o = 440 mM [Na+]I = 44 mM [K+]o : [K+]I = 0.05 [Na+]o : [Na+]I = 10 31 3/20/2017 Actual Vm may be anywhere between these: If Pk = 10 X Pna : 10 [20] + 1 [440] Vm = 58 log ----------------------10 [400] + 1 [44] = 58 log (640/4044) = -46.4 mV Membrane potential (mV) +58.0 ENa 0 -46.4 -75.0 Vm EK Complete mV +60 -------ENa 0 -70 -90 --------Vm ---------EK time 32 3/20/2017 Phases of Action Potential in nerve and skeleton muscle Concentration gradients exist across the plasma membrane. Specifically, there are ________. A. more sodium ions inside and more potassium ions outside the plasma membrane. B. more potassium ions inside and more sodium ions outside the plasma membrane. C. more sodium and potassium ions inside the plasma membrane than outside. D. equal concentrations of sodium and potassium ions outside the plasma membrane. 33 3/20/2017 The value of the typical nerve resting membrane potential is ________. A. B. C. D. –70 mV +30 mV –90 mV –55 mV The plasma membrane is more permeable to ________. A. sodium ions B. potassium ions 34 3/20/2017 The resting membrane potential depends on each item below, EXCEPT: A. the concentration gradient for sodium ions. B. the greater permeability of the plasma membrane to potassium ions. C. the greater permeability of the membrane to anions rather than cations. D. the greater number of potassium leak channels. The Na+/K+ pump transports ________. A. Na+ into and K+ out of the cell B. Na+ out of and K+ into the cell C. equal numbers of Na+ out of and K+ into the cell D. more K+ into than Na+ out of the cell 35 3/20/2017 ∆V This equation (Ohm’s law) states that: I = ----R A.The greater the voltage gradient, the higher is the current B.The greater the resistance, the higher is the voltage gradient C.The lower the current the larger is the resistance. D.The greater the voltage gradient, the lower is the resistance. For the 1st exam 1. Benchmarks Unit 1: Fluids and osmoregulation 2. Kidney calculate GFR, countercurrent, Hormonal regulation (ADH, Aldosterone) 3. Graphing, short essays 4. Tutorial 1: Solutes, solutions and osmolality. Aquatic environments 36 3/20/2017 Key Differences in Definition results from an environmental change Acclimation: occurs within an individual organism and changes within a lifetime change is reversible due to experimental conditions or can be in laboratory or controlled setting Acclimatization: occurs within an individual organism and changes within a lifetime change is reversible due to natural conditions Adaptation: occurs within a group of individuals (population) changes over several generations change is not reversible due to either natural or experimental conditions (artificial selection) genetic change and evolutionary response 37
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