Cell Membrane - Medical Sciences PDF

Dr Katja Vogt Cell Biology @katjetz [email protected] BSc School of Medicine Medical Sciences 3 Dr Katja Vogt  Dr Katja Vogt Cell membrane Learn...

Dr Katja Vogt Cell Biology @katjetz [email protected] BSc School of Medicine Medical Sciences 3 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 @katjetz [email protected] 6 BSc Medical Sciences  Dr Katja Vogt Cell homeostasis @katjetz [email protected] 7 BSc Medical Sciences  Dr Katja Vogt Cell Membrane Extracellular The lipid bilayer basic fluid structure Phospholipid bilayer Relatively impermeable barrier Hydrophilic head Thermodynamically stable Hydrophobic tail Hydrophobic Intracellular tail Phosphoglycerides Phospholipids Hydrophilic head Sphingolipids Cholesterol Phosphoglyceride 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  Dr Katja Vogt The fluidity of the membrane  Dr Katja Vogt Membranes structure Fluid mosaic model Membrane asymmetry  Dr Katja Vogt 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? @katjetz [email protected] 13 BSc Medical Sciences  Dr Katja Vogt What do we need to transport? 14 Cell Biology  Dr Katja Vogt Go with the flow - passive transport with the concentration gradient small molecules membrane simple facilitated diffusion diffusion @katjetz [email protected] 15 BSc Medical Sciences  Dr Katja Vogt Go against the flow - active transport against the concentration gradient need Energy small molecules ATP for example: Ca2+ transporter, CFTR @katjetz [email protected] 16 BSc Medical Sciences  Dr Katja Vogt Disease relevant transporters (examples) agent gene name disease GLUT1 Glut 1 deficiency syndrome sugars GLUT2 Fanconi Bickel Syndrome transport GULT9 renial hypouricemia-2 passive 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 inflammatory transport MRP1 Crohn disease mediators, drugs active DBP Graves disease vitamins ThTr1 Thiamin-responsive megaloblastic anemia syndrome PCFT Hereditary folate malabsorbtion CLCN5 Dents disease CFTR Cistric fribrosis ions KCNQ4 Nonsyndromic dominant defness nAChR Myasthenia gravis @katjetz [email protected] 17 BSc Medical Sciences  Dr Katja Vogt Cystric 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 (Dodge et al. 2007) in the UK Further reading: Harrisons principle of internal medicine, chapter 285  Dr Katja Vogt passive transport active transport simple facilitated diffusion diffusion small molecules @katjetz [email protected] 19 BSc Medical Sciences  Dr Katja Vogt Transport of large molecules: endocytosis & exocytosis against the concentration gradient complex machinery requiring the cytoskeleton and specific receptors Endocytosis Exocytosis @katjetz [email protected] 20 BSc Medical Sciences  Dr Katja Vogt Endocytosis “cell eating” 1. Phagocytosis large molecules; whole cells “cell drinking” 2. Pinocytosis fluids; small molecules 3. Receptor-mediated Triggered by endocytosis ligand signal  Dr Katja Vogt Phagocytosis  Dr Katja Vogt Receptor mediated endocytosis  Dr Katja Vogt Exocytosis Secreting and excretion of substances from the cell. 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 @katjetz [email protected] 25 BSc Medical Sciences  Dr Katja Vogt @katjetz [email protected] BSc Medical Sciences  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+ @katjetz [email protected] BSc Medical Sciences  Dr Katja Vogt Polarisation Because there is a potential difference across the cell membrane, the membrane is said to be polarised. If the membrane potential becomes more positive than it is at the resting potential, the membrane is said to be depolarised. If the membrane potential becomes more negative than it is at the resting potential, the membrane is said to be hyperpolarised. @katjetz [email protected] BSc Medical Sciences  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) @katjetz to concentration [email protected] BSc Medical Sciences  Dr Katja Vogt Action potential RMP = resting membrane potential @katjetz [email protected] BSc Medical Sciences  Dr Katja Vogt Action potential is a rapid depolarisation of the cell membrane potential. travels along the length of the cell membrane without a decrease in amplitude. obeys an all-or-nothing rule. is caused by the opening of voltage-gated ion channels ( see cell signalling session for details on the channels). can be divided into 4 phases: Initiation; Upstroke; Repolarisation and Refractory period @katjetz [email protected] BSc Medical Sciences  Dr Katja Vogt Action potential - phases Initiation: – A threshold that needs to be overcome to fire an action potential is around -60 to -50mV. – Once threshold is passed the action potential obeys an all-or-nothing rule. Upstroke – Once the threshold is reached, voltage-gated Na+ channels open, resulting in an influx of Na+ ions. – The channels are only open for milliseconds and go into an inactive state after that. Repolarisation – The same depolarisation stimulus, that opens the Na+ channels also opens voltage-gated K+ channels (they take longer to respond). The K+ channels open when the Na+ channels shut – resulting in a K+ efflux out of the cell. This conductance is so strong that the membrane hyperpolarises. Refractory period – By definition, the refractory period is a period of time during which a cell is incapable of repeating an action potential, so it starts after the threshold is passed. – In terms of action potentials, it refers to the amount of time it takes for an excitable membrane to be ready to respond to a second stimulus once it returns to a resting state. within the refractory period the Na+/K+ pumps restores the resting membrane potential @katjetz [email protected] BSc Medical Sciences  Dr Katja Vogt Summary What is a cell? 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 @katjetz [email protected] 44 BSc Medical Sciences  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&sectionid=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&sectionid=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 https://www.youtube.com/watch?v=SUyMRfuPQ_w https://www.youtube.com/watch?v=L4Tbi1ql-tU @katjetz [email protected] 45 BSc Medical Sciences