Lec 3-1 THE RESTING CELL MEMBRANE POTENTIAL PDF

MEMBRANES AND RECEPTORS MODULE SESSION 3 LECTURE 3.1 THE RESTING CELL MEMBRANE THE RESTING CELL MEMBRANE POTENTIAL Lecturer Dr. Safa Amir References Ganong, W.F., Review of Medical Physiology, 23rd Edition, McGraw-Hill, 2009, ISBN9780071605670 Guyton, A.C., Human Physi...

MEMBRANES AND RECEPTORS MODULE SESSION 3 LECTURE 3.1 THE RESTING CELL MEMBRANE THE RESTING CELL MEMBRANE POTENTIAL Lecturer Dr. Safa Amir References Ganong, W.F., Review of Medical Physiology, 23rd Edition, McGraw-Hill, 2009, ISBN9780071605670 Guyton, A.C., Human Physiology and Mechanisms of Disease, 6th Edition, W.B. Saunders, 1997, ISBN 0721632998 The objectives of this lecture are: to develop an understanding of the membrane potential in cells to outline how they are set up and how they may be changed by mechanisms involved in cellular signalling. understand the term equilibrium potential for an ion, and calculate its value form the ionic concentrations on either side of the membrane. Objective number 1 Development of an understanding of the membrane potential in cells The Membrane Potential ( objective number 1) All cells have an electrical potential (voltage) difference across their plasma membrane. This membrane potential provides the basis of signaling in the nervous system as well as in many other types of cells The resting membrane potential is the electrical potential difference across the plasma membrane of a normal living cell  Resting Potentials Membrane potentials are always expressed as the potential inside the cell relative to the extracellular solution. Membrane potentials are measured in millivolts Animal cells have negative membrane potentials at rest that range from –20 to – 90 mV. OBJECTIVE NUMBER 2 Outline how they are set up and how they may be changed by mechanisms involved in cellular signalling  Selective permeability of the cell membrane Membrane potentials are set up because the membrane is selectively permeable to different ions. The permeability of the membrane to ions occurs by way of channel proteins; membrane-spanning transport proteins that allow ions to permeate. ion channels are characterized by: 1. Selectivity: the channel lets through only one (or a few) ion species. Channels selective for Na+, K+, Ca2+ , Cl- 2. Gating: the channel can be open or closed by a conformational change in the protein molecule. 3. A high rate of ion flow that is always down the electrochemical gradient for the ion. Setting up the Resting Potential Ionic concentrations in a typical mammalian cell (mM): Intracellular Extracellular Na+ 10 mM Na+ 145 mM K+ 160 mM K+ 4.5 mM Cl - 3 mM Cl - 114 mM A- 167 mM A- 40 mM A- represents anions other than Cl-, including phosphate, amino acids, charged groups on proteins Na+ Na+ Cl- Cl- Organic Anions Organic anions K+ K+ Distribution of main ions  Ion Distribution Anions (-)  Large intracellular proteins  Chloride ions Cl- Cations (+)  Sodium Na+  Potassium K+ ~  Resting Membrane Potential + Cl- outside Na K+ + + + + + + + + + + + + + + + + + + + + + + Membrane - - - - - - - - - - - - - - - - - - - - - - inside A- Na+ K+ Cl- At rest the membrane has open K+ channels, so is selectively permeable to K+. K+ will begin to diffuse out of the cell down its concentration gradient. Since anions cannot follow, the cell will become negatively charged inside. This membrane movement potential of K+, and thewill oppose system willthe outward come into equilibrium.  Na+ 3 Na+ Na+ ATPase Cl- Cl- 2 K+ Organic Anions Organic anionsAnionic proteins are trapped Inside the K+ K+ cell Electrical disequilibrium across the cell membrane  membrane potential difference How does electrical charge separation occur?  The cell membrane Is an insulator There are more positive charges outside and more negative charges inside  Electrochemical gradient Electrical gradients and chemical gradients across the cell membrane Electrical force moves K+ into the cell (cell has more neg. charges) Chemical gradient favors K+ to leave the cell (K+ concentration is low outside) These forces reach a steady state  Membrane Potential Vm is the membrane potential (millivolts) Resting membrane potential for nerves and muscles is -40 mV to -90 mV The resting membrane potential is determined by K+ Objective number 3 understand the term equilibrium potential for an ion, and calculate its value form the ionic concentrations on either side of the membrane  Nernst Potential The potential across the cell membrane at which the net diffusion of ions across the cell membrane due to concentration gradient stops.  The Nernst equation For convenience, it is common to work out the constants RT/F and to convert from ln (natural logarithm) to log10: The voltage is given the symbol EK : the K+ equilibrium potential At 37 ºC : The Nernst equation allows you to calculate the membrane potential at which K+ will be in equilibrium, given the extracellular and intracellular K+ concentrations. The system will rapidly come into equilibrium so that the electrical (dotted line) and diffusional (solid line) forces balance one another and there is no net movement of K+. The membrane potential at which this occurs is called the potassium equilibrium potential or EK. It can be calculated from the Nernst equation: The equilibrium potential for an ion, Eion is given by the Nernst Equation where V is the membrane potential, R is the gas constant, T is the temperature in o K, Z the valency of K+ (+1), F is Faraday's number, and [K+]o and [K+]i are the outside and inside concentrations of K+. It is common to work out the constants and convert the natural logarithm to log10, giving, at 37oC: 63 The Nernst equation may be written for other ions as well, e.g. Na+, Ca2+, Cl-  Equilibrium Potential  RT [K ] E  K log  o ZF [K ] i R = gas constant F = Faraday constant T = temperature (K) Z = valence (charge) of ion ~  Equilibrium Potential  58mV [K ] E  K log  o Z [K ] i K+: z = +1 Cl-: z = -1 Mg++: z = +2  Equilibrium Potential Constants never change Assume 25 oC (298 oK) Use log10 ~ 20 E  58mV  log K  75mV 400 It is common to work out the constants and convert the natural logarithm to log10, giving, at 37oC:  Equilibrium(Nernst) Potential for K+ KK+K outside = 4.0 m Eq/L }61x log 35= –94mv K+ inside = 140 m Eq/L  Equilibrium Potential  RT [ Na ] E  Na log  o ZF [ Na ] i 440 E  58mV  log Na  55mV 10 50  Equilibrium (Nernst) Potential for Na+ Na+ outside = 142 m Eq/L } 61x log 0.1 = +61mv Na+ inside = 14 m Eq/L K+ channels are open during the resting membrane potential. Cardiac muscle, nerve cells: Resting potential is quite close to EK (~ - 60 to - 90 mV). Not exactly at EK (less negative): Skeletal muscle :. Resting potential ≈ -90 mV. Close to both ECl and EK At the equilibrium potential for Na+ Artificial cell, Na+ is leaving because the inside became + after the Movement of Na+  Changing Membrane Potentials Changes in membrane potential underlie many forms of signalling between and within cells. Examples: 1. Action potentials in nerve and muscle cells 2. Triggering and control of muscle contraction 3. Control of secretion of hormones and neurotransmitters 4. Transduction of sensory information into electrical activity by receptors 5. Postsynaptic actions of fast synaptic transmitters THANKS