Week 5 - Cell Membrane PDF

Dr Katja Vogt Molecular Cell Biology @katjetz School of Medicine [email protected] [email protected] BSc Medical Sciences 1 Dr Katja Vogt  Dr Katja Vogt Cell membrane Learning ob...

Dr Katja Vogt Molecular Cell Biology @katjetz School of Medicine [email protected] [email protected] BSc Medical Sciences 1 Dr Katja Vogt  Dr Katja Vogt Cell membrane Learning objectives ☑ Explain the structure and function of the cell membrane ☑ Discuss membrane permeability transport ☑ Interpret resting and action membrane potential the corresponding currents [email protected] 3 BSc Medical Sciences  Dr Katja Vogt Cell homeostasis 4  Dr Katja Vogt Cell Membrane Extracellula r The lipid bilayer basic fluid structure Phospholipid bilayer Relatively impermeable barrier Hydrophilic head Thermodynamically Hydrophobic Hydrophobic Intracellula tail tail stable r Hydrophilic Phospholipi head Phosphoglycerides ds Sphingolipids Cholesterol Phosphoglyceri de Polar head groups Cholesterol- stiffened region More fluid region Cholesterol  Dr Katja Vogt The composition of the membrane Proteins Carbohydrates Integral or Peripheral membrane proteins The fluidity of the membrane  Membranes structure Fluid mosaic model Membrane asymmetry  Membrane functions 1. Compartmentalisation 2. Scaffold for biochemical activities 3. Platform to exchange contents with the environment  Dr Katja Vogt 3. Platform to exchange contents with the environment Why? - to maintain homeostasis What do we need to transport? 1 0  Dr Katja Vogt What do we need to transport? [email protected] 1 BSc Medical Sciences 1  Dr Katja Vogt Go with the flow - passive transport with the concentration gradient small molecules membrane simple facilitated diffusion diffusion [email protected] 1 BSc Medical Sciences 2  Dr Katja Vogt Go against the flow - active transport against the concentration gradient need Energy small molecules ATP for example: Ca2+ transporter, CFTR [email protected] 1 3  Dr Katja Vogt Disease relevant transporters (examples) agent gene name GLUT1 disease Glut 1 deficiency syndrome transport sugars GLUT2 Fanconi Bickel Syndrome passive GULT9 renial hypouricemia-2 FATP2 Milder variant of x-linked Adrenolucodistrophy lipids FATP4 Ichtyosis prematurity syndrome (IPS) nucleotides ENT3 Familial Histiocysis Syndrome and Familial Rosai-Dorfmann disease SGLT1 Glucose-galactose malabsorbtion sugars SGLT2 renal glucosuria transport inflammatory mediators, MRP1 Crohn disease drugs active DBP Graves disease vitamins ThTr1 Thiamin-responsive megaloblastic anemia syndrome PCFT Hereditary folate malabsorbtion CLCN5 Dents disease CFTR Cystic fibrosis ions KCNQ4 Nonsyndromic dominant defness nAChR Myasthenia gravis [email protected] 1 4  Dr Katja Vogt Cystic fibrosis Malfunctioning chloride channel —> H2O does not follow the Cl- out of the cell leads to thickening of the mucus Affects multiple epithelial tissues specially in lungs, liver, kidneys, intestines Incidence of one in 2,500 live births Further reading: Harrisons principle of internal medicine, chap Dr Katja Vogt  Dr Katja Vogt passive transport active transport simple facilitated diffusion diffusion small molecules 1 7  Dr Katja Vogt Transport of large molecules: endocytosis & exocytosis against the concentration gradient complex machinery requiring the cytoskeleton and specific receptors Endocytosi s Exocytosi s [email protected] 1 8  Dr Katja Vogt Endocytosis “cell eating” 1.Phagocytosis large molecules; whole cells “cell drinking” 2.Pinocytosis fluids; small molecules 3.Receptor- Triggered by mediated ligand signal endocytosis Phagocytosis Receptor mediated endocytosis  Dr Katja Vogt Exocytosis Secreting and excretion of substances from the cell. Constitut ive Constitutive secretory pathway Regulated secretory pathway Lysosomal secretory pathway  Dr Katja Vogt passive transport active transport simple facilitated endocytosis exocytosis diffusion diffusion small molecules large molecules 2 3  Dr Katja Vogt Membrane potential All cells have a membrane potential The difference in electrical potential across the membrane of a biological cell between the outside and inside Always defines the inside; i.e. -70mV means the interior of the cell is negative. Usually between -90 and +40mV in human cells The major ions that influence the membrane potential are K+, Na+, Cl-, Ca2+ [email protected]  Dr Katja Vogt Polarisation Membranes can be polarised due to the potential difference across the cell membrane Depolarised membranes have a more positive potential compared to the resting membrane potential Hyperpolarised membranes have a more negative potential compared to the resting membrane potential [email protected]  Dr Katja Vogt Ion concentrations & charges Approximate extra- and intracellular concentrations K+o 5mM K+i 100mM Na+o 150mM Na+i 15mM Ca2+o 2mM Ca2+i 0.0002mM Cl-o 150mM Cl-i 13mM (The major intracellular Direction of ion anion is PO42-, but no movement due channels) to concentration [email protected]  Dr Katja Vogt Action potential RMP = resting membrane potential [email protected]  Dr Katja Vogt Summary How does a cell membrane work? Why do we need transport across the membrane and how do cells achieve this? What is a membrane and action potential and how does is occur? MBBS Learning outcomes: Recognise the key feature of the typical eukaryotic cell Outline the physiological action of neurotransmission, neurotransmitters and pathways such as reflexes Demonstrate an understanding of neural cell signal transduction and signal transmission and the neuromuscular junction [email protected] 2 8  Dr Katja Vogt Reading list “Essential Cell Biology”- Alberts, B. et al. 2014 Chapter 17 “Pathologic Basis of Disease” – Kumar et al. 2010 p1322-23 "Overview of Cellular Physiology in Medical Physiology." Ganong's Medical Physiology Examination & Board Review Eds. Kim E. Barrett, et al. New York, NY: McGraw-Hill, , http://accessmedicine.mhmedical.com/content.aspx?bookid=2139&section id=160311582. Histology & Cell Biology, Chapter 2 & 3, Examination & Board Review, 5e Ed. Douglas F. Paulsen. New York, NY: McGraw-Hill, 2010, http://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectioni d=42045296. Swagatika Sahoo, Maike K. Aurich, Jon J. Jonsson and Ines Thiele; Membrane transporters in a human genome-scale metabolic knowledgebase and their implications for disease; Front. Physiol., 11 March 2014 https://www.youtube.com/watch?v=AcrqIxt8am8 [email protected] https://www.youtube.com/watch?v=SUyMRfuPQ_w 2 9