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Melvin Bae 2nd Faculty of medicine 2014. Basic principles  Ion flux; driven by force of diffusion and/ or electrostatic forces  Ions diffuse through.

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Presentation on theme: "Melvin Bae 2nd Faculty of medicine 2014. Basic principles  Ion flux; driven by force of diffusion and/ or electrostatic forces  Ions diffuse through."— Presentation transcript:

1 Melvin Bae 2nd Faculty of medicine 2014

2 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  Ion channels in each of living cell

3  Ions flow „downhill“ towards the concentration gradient = CHANNEL  Ions flow „uphill“ against the concentrationgradient (energy needed) = PUMP/TRANSPORTER  Membrane potential  via Goldman-Hodgkin-Katz equation (GHK equation) (expansion of Nernst equation = only single Ion type) Over 300 diferent ion channel types  Aprox. 10 7 ions / per second / per channel Basic principles

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.) hormone secretion, neurotransmitter release, muscle contraction

9 Morphology of ion channels

10 Sodium channels  9 known in human being (E.g. Neurons, myocites, glia cells )  big integral protein structure, ca 300kD, aprox 0,3-0,5 nm diameter  Pore just big enough for 1 Na+ with one associated H2O molecule

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


13 Potassium Channels

14 1. (Ion) Ligand gated (e.g. Ca++) 2. Mechanical (e.g. tip links; stereocilia; inner hair cell -> ear ) 3. G Protein –(e.g. in cardiac muscle) 4. (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)

15 Potassium Channels  Example of Potassium-channel regulated hormone secretion in the Beta Cells in the Langerhans islands (pancreas)

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

17 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

18 Patch clamp method

19 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

20 5 types of Voltage gated Ca2+ channels Type L – Type (Long-lasting) High Voltage Skelettal muscle, smooth muscle, osteoblasts P (Purkinje) HVPurkinje cells N (Neural) HVBrain and PNS, (presynaptic terminal ) R (Residual) Intermediate Voltage Cerebellar granule cells T (Transient) Low VoltagePacemaker activity, osteocytes

21 Presynaptic terminal

22 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

23 Ligand gated Ca 2+ Channels  Examples:  cAMP ( of myocard cells)  IP3 (Inositol Triphosphat)  for IC Ca 2+ depots  Ion channels in Sperms ( Cation) - > functionally necessary for fertility and also fertilization  Ca 2+ 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.

24 Cardiac muscle

25 Already if Ca 2+ drops 50% -> muscle tetany (lethal if respiratory) Skeletal muscle

26 Chloride channels

27  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 ) Cl - channels

28 - transepithelial salt transport,  Or cystic fibrosis transmembrane conductance regulator ( CFTR) gene   cystic fibrosis  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. Cl - channels

29 Thank you for your attention !

30 Ion channel openers / closers OPENERS  Diazoxide -vasodilator used for hypertension, smooth muscle relaxing activity CLOSERS  Amiodarone - Used to treat cardiac arrhythmias, prolonging the repolarization

31 Yellow – in Grey - out

32 Sources = evolution of those channels homepage: Alexander Chew:Florida State University;BSC5936;February 2005 Source: Mizutani S, "Milestones in the Evolution of the Study of Arrhythmias" Literature: (german book edition) Silbernagl; Taschenatlas Physiologie guyton & Hall : textbook medical physiology (german book edition) Golenhofen; Basislehrbuch physiologie (4th edition)

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