Neuronal Membrane Lecture PDF

The Neuronal Membrane Dr Amar Daud Iskandar Abdullah  Lecture outline Membrane structure and function Components of plasma membrane Function of membrane proteins Overview of membrane transport  Learning objectives  Describe the structure and functions of plasma membr...

The Neuronal Membrane Dr Amar Daud Iskandar Abdullah  Lecture outline Membrane structure and function Components of plasma membrane Function of membrane proteins Overview of membrane transport  Learning objectives  Describe the structure and functions of plasma membrane  Identify the major components of the plasma membrane  Understand the different types of membrane proteins and explain their function  Explain how various forms of membrane transport work  Plasma membrane All cells, including neurons and glia, enclosed by a plasma membrane Regional differences in composition and concentration of membrane proteins are key to neuronal function http://cellbiology.med.unsw.edu.au/units/images/Cell_membrane.png  Composition of plasma membrane Fluid lipid bilayer embedded with proteins – Most abundant lipids are phospholipids Small amount of carbohydrates – On outer surface only Cholesterol – Tucked between phospholipid molecules – Contributes to fluidity and stability of cell membrane Proteins – Attached to or inserted within lipid bilayer – Integral and peripheral proteins Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning  Structure of phospholipid molecule Polar head - containing negatively charged phosphate group - hydrophilic (water-loving) → interact with water molecule 2 nonpolar fatty acid tails - hydrophobic (water-fearing) →will not mix with water Hydrophobic tail bury themselves in the center Hydophilic heads line up both sides, in contact with water Sherwood, L. (2012). Fundamentals of Human Physiology, Brooks/Cole-Cengage Learning Plasma membrane components Cell membrane consists of Cholesterol Phospholipids Carbohydrates Proteins together form together form together form Lipid bilayer Glycolipids Glycoproteins function as functions include Selective barrier between cytosol and external environment Structural Cell recognition Immune stability response Modified from Silverthorn (2010) Human Physiology: An Integrated Approach, 5th Edition, Pearson  Functions of plasma membrane Physical barrier – separate intracellular fluid and extracellular fluid (ECF) Exchange of materials with the environment – entry of ions and nutrients into cell – elimination of cellular waste and release of products Communication between cell and environment – surface proteins respond and recognize other molecules Structural support – cell shape maintained by cytoskeletal proteins attached to membrane proteins  Membrane carbohydrate function Function as “self” markers Allow cells to identify themselves as belonging to you Allows cells to identify cells of the same type Carbohydrate-containing surface markers - used during tissue formation – To ensure that the same type of cells are being used and tissues do not overlap  Membrane protein function Channels  Leak channels  Gated channels Carrier (transport)  Selective transport Docking-marker acceptors / receptors Membrane-bound enzymes Cell adhesion molecules (CAMs)  Integrin / cadherin http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/MembraneProteins.gif Cell surface markers Different types of membrane proteins Membrane proteins Sherwood, L. (2012). Fundamentals of Human Physiology, Brooks/Cole-Cengage Learning  Fluid mosaic model of membrane structure Main properties of lipid bilayer are included in model of fluid mosaic: 1. Heterogeneity in the plane horizontal and vertical 2. Fluid state of most lipids at physiological conditions 3. Translation and rotation movement of membrane molecules Dynamic properties of biological membranes enable movement and mutual interactions of membrane proteins Membrane lipids participate in signal transduction process  Overview of membrane transport Selective permeability  Plasma membrane controls what enter and exits the cell Determined by two properties:  Size of the particle  Solubility of the particle in lipids Can be unassisted or assisted transport Passive or active membrane transport  Types of membrane transport Unassisted membrane transport – Diffusion – Osmosis Assisted membrane transport – Carrier-mediated transport – Facilitated transport – Active transport → Primary and secondary Transportation of small molecules across the membrane These teaching re protected under the Copyright Act 1987. Duplication, in any form, including digitally, is punishable offence. Transportation of small molecules across the membrane Na+/K+ - Across ATPase or membra Na+/K+ pump ne pores Ca2+ Pumps Leak Channel Na+/Ca2+ Potassium channel Exchanger Sodium channel Cl-Transporters Voltage-Gated Potassium Voltage-Gated Sodium Calcium Channels Ligand-gated ion Types of membrane transport http://themedicalbiochemistrypage.org/membranes.php  Diff usion Net movement from an area of higher concentration to an area of lower concentration Does not require energy, passive process Diffusion through a membrane: Sherwood, L. (2012). Fundamentals of Human Physiology, Brooks/Cole-Cengage Learning  Diff usion Fick’s law of diffusion - factors that influence the rate of diffusion: Magnitude of concentration gradient Surface area of membrane Lipid solubility of substance Molecular weight of substance Distance across membrane  Osmosis Diffusion of water across a selectively permeable membrane Aquaporins  protein channels that allow water the diffuse in and out of cell  Increases membrane permeability to water  Osmosis Tonicity  Refers to the effect the solution on cell volume  Determines whether cell remains same size, swells, or shrinks when a solution surrounds the cell Hypertonic – Higher concentration of nonpenetrating solutes than normal body cells – Cells shrink as they lose water by osmosis Hypotonic – Lower concentration of nonpenetrating solutes than normal body cells – Water enters cell causing cell to swell or perhaps rupture Isotonic – Same concentration of nonpenetrating solutes as normal body cells, water movement at equilibrium – Cell volume remains constant, retains its normal shape Tonicity and osmotic water movement Sherwood, L. (2012). Fundamentals of Human Physiology, Brooks/Cole-Cengage Learning  Carrier-mediated transport Require a conformational change as transport protein Transport of small hydrophilic molecules across membrane Can be active or passive Characteristics that determine the kind and amount of material that can be transferred across the membrane  Specificity  Saturation  Competition  Facilitated diff usion Similar to simple diffusion, but requires a carrier Facilitate transfer of a particular substance across membrane from high to low concentration Passive carrier-mediated transport e.g. transport of glucose – glucose transporter (GLUT) Facilitated diff usion Sherwood, L. (2012). Fundamentals of Human Physiology, Brooks/Cole-Cengage Learning  Active transport Carrier protein to transfer substance against its concentration gradient Requires energy Primary active transport  Directly utilizes ATP to drive transport of molecules against concentration gradient Secondary active transport  Utilizes potential energy stored in electrochemical gradients of ions to drive transport of another molecule (cotransport)  Driven by an ion concentration gradient established by a primary active transport system Primary active transport - Na+-K+-ATPase pump  Secondary active transport Sherwood, L. (2012). Fundamentals of Human Physiology, Brooks/Cole-Cengage Learning Co-transport molecules across the plasma membrane  Same direction (symport)  Opposite directions (antiport)  Secondary active transport Sodium and glucose cotransporter (SGLT)  Vesicular transport Transport of large molecules across membrane Formation of membrane-enclosed vesicles Active method of membrane transport Two types of vesicular transport  Endocytosis  Exocytosis  Endocytosis Process by which substances move into cell Phagocytosis – selective uptake of multimolecular particles (e.g. bacteria and cellular debris) Pinocytosis – nonselective uptake of ECF fluid Receptor-mediated endocytosis – selective uptake of large molecule (e.g. protein) Stanfield, C.L. (2013) Principles of Human Physiology, 5th Edition, Pearson  Exocytosis Process by which substance transported out of cell Provides mechanism for secreting large polar molecules Enables cell to add specific components to membrane Stanfield, C.L. (2013) Principles of Human Physiology, 5th Edition, Pearson Type of ion transportation at the neural membrane Different ions Energ Same y is direction neede Symport d Passive Same ion Different Both ions directi Both ons directions Unipor Antiport  Membrane Potentials Different types of potentials:  Equilibrium potential  Resting membrane potential (RMP)  Graded potentials  Action potential  Basic Electrical Concepts Terminologie Definition In neurons? s Current (I) Charge flowing past Involves cations such as K+, Na+ (the flow) a and Ca2+ single point. and anions such as Cl-. Potential Work required to Resting membrane potential is different separate -70mV, (the electrical Which means it has a 70mV voltage) charges, which is difference between electrical measured potential outside its membrane between 2 points and the electrical potential in millivolts inside its membrane (mV). With inside being more electrically negative. Conductance Extent to which a A membrane with few open ion (g) (the given pathway channels ability to allows charge to  high resistance  low flow) flow. conductance. g=1/R A membrane with many (R=resistance) open ion channels  low resistance  high Ions move down the concentration gradient Ions move down the concentration gradient via diffusion. From more concentrated to less concentrated compartment. When they achieve equilibrium, the net movement of ions becomes 0.  Ions move down the electrical gradient The charges of the ions form electrical gradients between the inner and outer compartment of the cell. Ions will be more attracted to the opposite charges. The positive repels and the negative attracts. When they achieved equilibrium, net movement In reality…. Concentration and electrical gradients affect the ion movement in the opposite direction. How can we calculate the directionality of ions movement?  Equilibrium Potential – Nernst Potential 1. Nernst potential = Equilibrium potential = The difference in the concentration of an ion inside and outside of a cell generates an electrochemical potential 2. For a specific ion, the electrical potential difference that exactly counterbalances diffusion due to the concentration difference is called the equilibrium potential for that specific ion. 3. Potential at which an ion’s flux down its concentration gradient exactly balances flux down its electrical gradient. 5 4. The basis ofrefers Equilibrium neuronal excitability, to the fact that via the ion netmovement ion flux at a downhill. of particular(diffusion ions from high to voltage is low concentrations) zero. into and That is, the outward andout inward 6 of a neuron. Provides rates themovement of ion free energy to the are drive otherthe same; ions ionand fluxsmall is in molecules,. as such neurotransmitters, equilibrium. uphill (against their concentration electrochemical / Equilibrium Potential for Potassium (K+) Physiologic distribution of ions (Equilibrium/Nernst Potential) Factors that influence the development of potential different Concentration gradient of ions Electrical potential different The state of ion channels The presence of electrogenic pump or Na+/K+ pump The presence of minute amount of negative ions in the cell (e.g. phosphate ions)  Resting Membrane Potential (RMP) Steady-state membrane Results primarily from constant net flux of K+ ions of potential the neuron and smaller net flux of Na+ in the neuron. Depends on action of Na+/K+ ATPase pump that maintain both K+ and Na+ concentration gradients. Does not change with minor perturbations such as action potential generation. Resting membranes are most permeable to K+ Changes in ion concentrations affect RMP  significant clinical impact (e.g. KCl) Resting Membrane Potential (RMP) is about -70mV  Resting Membrane Potential (in reality) These teaching materials are protected under the Copyright Act 1987. Duplication, in any form, including digitally, is prohibited by law  Summary  Describe the structure and function of plasma membrane  Describe the major components of the plasma membrane and their functions  Identify the different types of membrane proteins and their role  Explain how various forms of membrane transport work