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Ion Channels

Ion Channels. Melvin Bae 2nd F aculty of medicine 2014. Basic principles. Ion flux; driven by force of diffusion and/ or electrostatic forces Ions diffuse through channels ( „ Leak channels “ ) =constantly open -> no further impuls needed Gated channels -> signal needed

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Ion Channels

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  1. Ion Channels Melvin Bae 2nd Faculty of medicine 2014

  2. Basic principles • Ion flux; driven by force of diffusionand/ or electrostatic forces • Ions diffuse through channels ( „Leak channels“) =constantly open -> no further impuls needed • Gated channels • -> signal needed • Ion channels in each of living cell

  3. Basic principles • Ions flow „downhill“ towards the concentration gradient =CHANNEL • Ions flow „uphill“ against the concentrationgradient (energy needed) = PUMP/TRANSPORTER • Membranepotential  via Goldman-Hodgkin-Katz equation (GHK equation) (expansion of Nernst equation = only single Ion type) Over 300 diferent ion channel types • Aprox. 107 ions / per second / per channel

  4. Basic mechanisms

  5. Silbernagl; Taschenatlas Physiologie

  6. Main functions • 1.) Ion concentraion sets up resting potential : • Na+ open  Depolarization • K+ open  Re- and Hyperpolarization

  7. Main functions • 2.) Volume Regulation and Salt balance: • Ion flux controles electrolyte distribution • Across epithel (basal labyrinth - typical) • Examples : gut, kidney, sweat glands or the choroid plexus.

  8. Main functions • 3.) hormonesecretion, neurotransmitterrelease, musclecontraction

  9. Morphology of ion channels

  10. Sodium channels • 9 known in human being (E.g. Neurons, myocites, gliacells ) • big integral proteinstructure, ca 300kD, aprox0,3-0,5 nmdiameter • Pore just bigenoughfor 1 Na+ withoneassociated H2O molecule

  11. Compartements of a channel • - Ion conductiong pore • Gate • Sensor

  12. Potassium Channels

  13. Potassium Channels • (Ion) Ligand gated (e.g. Ca++) • Mechanical (e.g. tip links; stereocilia; inner hair cell -> ear ) • G Protein –(e.g. in cardiac muscle) • (Metabolite) Ligand (e.g ATP reactive Beta cells) • Voltage gated K+ channels , only have open – closed state • ( Na+ =O/C/I) Blockers -> Tetraethylamoniom closes K+ Channels ; -> further more over 40 peptides from scorpion toxins; -> Apamin (Toxin of bees)

  14. Potassium Channels • Example of Potassium-channel regulated hormone secretion in the Beta Cells in the Langerhans islands (pancreas)

  15. Resting potential Necessary to maintain the electrochemical gradient : pumps and transporters

  16. Patch clamp method • Refinement of voltage clamp method by Hodgkin and Huxley – nobel price (1952) • Possible to measure selectively the Ion current through channels • Hollow end pipette 0,3-3 micrometer -> small membrane area selcected/torn out and isolated • Similar to the programm which we had in class !! Experiments with channel blocking drugs: • -> Tetradotoxin = blocks Na channels • -> Tetrathylammonium = blocks K Channels

  17. Patch clamp method

  18. Calcium channels e.g. In Cardiac and smooth muscle cells, Presynpatic terminals etc. Flux inside the cell/ to ER Ca2+ (free) EC= 2.5 mmol/L IC = 0.1 micromol/L

  19. 5 types of Voltage gated Ca2+ channels

  20. Presynaptic terminal

  21. Ligand gated Ion channel in Postsynaptic terminal • Cation channel ( Na+ or K+) • Lined with neg. charge, entrance becomes a bit larger • lets e.g. hydrated Na+ ions inside - -> excitatory • Anion channel (Cl-) -Pos charged, opens , influx of Cl- - ->Inhibitory

  22. Ligand gated Ca2+ Channels • Examples: • cAMP ( of myocard cells) • IP3 (Inositol Triphosphat)  for IC Ca2+ depots • Ion channels in Sperms ( Cation) -> functionally necessary for fertility and also fertilization  Ca2+ can function itself as an intracellulary transmitter which opens K+ channels or „fast“ Na+ channels (Silbernagl) Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.

  23. Cardiac muscle

  24. Skeletal muscle Already if Ca2+ drops 50% -> muscle tetany (lethal if respiratory)

  25. Chloride channels

  26. Cl- channels • Approximately 13 types • Neurones e.g. GABA ligand gated • Skeletal, cardiac and smooth muscle, • Cell volume regulation • E.g. CLC type (10-12 transmembrane helices) • -> CLC1 involved in reestablising resting membrane potential in skeletal muscle cells • Also -> solute concentration mechanism in the kidneys (abnormal function in thick ascending loop of Henle, associated with Bartter´s syndrom renal salt wasting )

  27. Cl- channels - transepithelialsalttransport, • Orcysticfibrosistransmembraneconductanceregulator (CFTR) gene •  cysticfibrosis • Genetic disorder • Gland secretions are abnormally thick • Chloride Ion Channels may be targeted as a treatment for some Respiratory Diseases by regulating abnormal mucus production.

  28. Thank you for your attention !

  29. Ion channel openers / closers OPENERS • Diazoxide -vasodilatorusedforhypertension, smooth musclerelaxingactivity CLOSERS • Amiodarone - Usedtotreatcardiacarrhythmias , prolongingtherepolarization

  30. Yellow – in Grey - out

  31. Sources http://www.creative-biogene.com/images/Ion-Channel.jpg http://en.wikipedia.org/wiki/Membrane_potential#mediaviewer/File:Basis_of_Membrane_Potential2.png http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14615258/f1_marban_415213a-f1.2.jpg http://www1.appstate.edu/~kms/classes/psy3203/Ear/hair_cell_tip.jpg http://www.medbio.info/images/Time%203-4/wpeozyop.gif http://upload.wikimedia.org/wikipedia/commons/thumb/e/e0/Synapse_Illustration2_tweaked.svg/2000px-Synapse_Illustration2_tweaked.svg.png https://www3.nd.edu/~aseriann/nak.gif http://www.uibk.ac.at/pharmazie/pharmakologie/images/cachannel.gif?m=e http://www.neurology.org/content/68/3/233/F1.large.jpg http://en.wikipedia.org/wiki/Sodium_channel#mediaviewer/File:Sodium_channel_phylogram.png = evolution of those channels homepage: Alexander Chew:Florida State University;BSC5936;February 2005 http://upload.wikimedia.org/wikipedia/commons/4/45/GABAA-receptor-protein-example.png http://cbsnews1.cbsistatic.com/hub/i/r/2010/09/22/86b3c5fb-a643-11e2-a3f0-029118418759/resize/620x465/9f5987c0e770cce5ce393581bd1aac6e/sperm_1.jpg http://upload.wikimedia.org/wikipedia/commons/8/81/1ots_opm.png Source: Mizutani S , "Milestones in the Evolution of the Study of Arrhythmias" http://circep.ahajournals.org/content/2/2/185/F1.large.jpg Literature: (german book edition) Silbernagl; Taschenatlas Physiologie guyton & Hall : textbook medical physiology (german book edition) Golenhofen; Basislehrbuch physiologie (4th edition)

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