Kapitoly zKapitoly z neurofyziologie smyslneurofyziologie smyslůů NeurofyziologieNeurofyziologie Ambice: PochopenAmbice: Pochopeníí psychikypsychiky ččlovlověěka a jejka a jejíích poruch.ch poruch. MolekulMolekuláárnrníí neurovneurověědydy NeurofarmakologieNeurofarmakologie ZobrazovacZobrazovacíí metodymetody BouBouřřlivý rozvoj:livý rozvoj: Nobel prices related to neuroscience 1901 Wilhelm Conrad Röntgen (Germany) "in recognition of the extraordinary services he has rendered by the discovery of the remarkable rays subsequently named after him" 1904 Ivan Petrovich Pavlov (Russia) "in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged" 1906 Camillo Golgi (Italy) and Santiago Ramón y Cajal (Spain) "in recognition of their work on the structure of the nervous system" 1909 Emil Theodor Kocher (Switzerland) "for his work on the physiology, pathology and surgery of the thyroid gland" 1914 Robert Bárány (Vienna) "for his work on the physiology and pathology of the vestibular apparatus" 1920 Chemistry: Walther Hermann Nernst (Germany) "in recognition of his work in thermochemistry" 1932 Sir Charles Scott Sherrington (Great Britain) and Edgar Douglas Adrian (Great Britain) "for their discoveries regarding the functions of neurons" 1935 Hans Spemann (Germany) "for his discovery of the organizer effect in embryonic development" 1936 Sir Henry Hallett Dale (Great Britain) and Otto Loewi (Great Britain) "for their discoveries relating to chemical transmission of nerve impulses" 1944 Joseph Erlanger (USA) Herbert Spencer Gasser (USA) "for their discoveries relating to the highly differentiated functions of single nerve fibres" 1949 Walter Rudolf Hess "for his discovery of the functional organization of the interbrain as a coordinator of the activities of the internal organs" 1949 Antonio Caetano de Abreu Freire Egas Moniz "for his discovery of the therapeutic value of leucotomy in certain psychoses" 1952 Physics: Felix Bloch (USA) and Edward Mills Purcell (USA) "for their development of new methods for nuclear magnetic precision measurements and discoveries in connection therewith" 1961 Georg von Békésy (USA/Hungary)"for his discoveries of the physical mechanism of stimulation within the cochlea" 1962 Francis Harry Compton Crick (Great Britain), James Dewey Watson (USA) and Maurice Hugh Frederick Wilkins (Great Britain) "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material" 1963 Sir John Carew Eccles (Australia), Alan Lloyd Hodgkin and Andrew Fielding Huxley (Great Britain) "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane" 1967 Ragnar Granit (Sweden/Finland), Haldan Keffer Hartline (USA) and George Wald (USA) "for their discoveries concerning the primary physiological and chemical visual processes in the eye" Robert W. Holley (USA), Har Gobind Khorana (USA) and Marshall W. Nirenberg (USA) "for their interpretation of the genetic code and its function in protein synthesis 1970 Sir Bernard Katz (Great Britain), Ulf von Euler (Sweden) and Julius Axelrod (USA) "for their discoveries concerning the humoral transmittors in the nerve terminals and the mechanism for their storage, release and inactivation" 1972 Physics: John Bardeen (USA), Leon Neil Cooper (USA) and John Robert Schrieffer (USA)"for their jointly developed theory of superconductivity, usually called the BCS-theory" [Professor Cooper was Director of Brown University's Center for Neural Science.] 1973 Karl von Frisch (Germany), Konrad Lorenz (Austria) and Nikolaas Tinbergen (Great Britain) "for their discoveries concerning organization and elicitation of individual and social behaviour patterns" 1973 Physics: Brian David Josephson (Great Britain) "for his theoretical predictions of theproperties of a supercurrent through a barrier, in particular those phenomena which are generally known as the Josephson effects" 1976 Baruch S. Blumberg (USA) and D. Carleton Gajdusek (USA) "for their discoveries concerning new mechanisms for the origin and dissemination of infectious diseases" 1977 Roger Guillemin and Andrew Schally for their discoveries concerning "the peptide hormone production of the brain" 1977 Rosalyn Yalow for "the development of radioimmunoassays of peptid hormones" 1979 Allan M Cormack and Godfrey Newbold Hounsfield for the "development of computer assisted tomography" 1981 Roger W. Sperry, for his discoveries concerning "the functional specialization of the cerebral hemispheres" 1981 David H. Hubel and Torsten N. Wiesel, for their discoveries concerning "visual system". 1986 Stanley Cohen (USA) Rita Levi-Montalcini (Italy/USA)"for their discoveries of growth factors" 1991 Erwin Neher (Germany) Bert Sakmann (Germany) "for their discoveries concerning the function of single ion channels in cells" 1991 Chemistry: Richard R. Ernst (Switzerland) "for his contributions to the development of the methodology of high resolution nuclear magnetic resonance (NMR) spectroscopy" 1994 Alfred G. Gilman (USA) Martin Rodbell (USA) "for their discovery of G-proteins and the role of these proteins in signal transduction in cells" 1997 Stanley B. Prusiner, in Physiology or Medicine for his discovery of "prions - a new biological principle of infection" 1997 Chemistry: Paul D. Boyer (USA) and John E. Walker (Great Britain) "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)" 1997 Jens C. Skou (Denmark) "for the first discovery of an ion-transporting enzyme, Na+, K+-ATPase" 1998 Robert F. Furchgott (USA)Louis J. Ignarro (USA) and Ferid Murad (USA) "for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system" 2000Arvid Carlsson, Paul Greengard and Eric Kandel for their discoveries concerning "signal transduction in the nervous systém 2003 Paul C. Lauterbur Sir Peter Mansfield for their discoveries concerning magnetic resonance imaging 2004 Richard Axel, Linda Buck for their discoveries of odorant receptors and the organization of the olfactory system http://http://nobelprizenobelprize..orgorg//medicinemedicine//laurelaure atesates/1981//1981/ NeurofyziologieNeurofyziologie Studium nervových a doprovodných buněk, způsobu jak jsou sestaveny do funkčních celků, které vedou, zpracovávají, ukládají informaci a zprostředkují chování. http://www.physpharm.fmd.uwo.ca/undergrad/medsweb/ http://entochem.tamu.edu/index.html http://web.neurobio.arizona.edu/gronenberg/nrsc581/index.html http://www.biol.sc.edu/~vogt/courses/neuro/neurobehavior.html http://instruct1.cit.cornell.edu/courses/bionb424/links.htm http://nelson.beckman.uiuc.edu/courses/neuroethol/ http://www.blackwellpublishing.com/matthews/default.html http://www.hhmi.org/biointeractive/vlabs/neurophysiology/index.html Internet a něco z jeho neomezené nabídky: Kapitoly z neurofyziologie smyslů – výběr kapitol Fyziologie membrán: - klidový potenciál - akční potenciál - iontové kanály - šíření signálů a synapse Fyziologie smyslů: - obecné principy - čich a chuť - hmat a sluch - zrak a další smysly Psychofyziologie: - zpracování zrakové informace - učení a paměť - chování, neuroetologie MateriMateriáály, prezentace,ly, prezentace, nnáávaznosti na pvaznosti na přředmedměěty,ty, hodnocenhodnoceníí.. Předávání a zpracování informací: elektro - chemická spolupráce Fyziologie membrFyziologie membráán:n: potencipotenciááll Klidový potenciál Gibbs-Donnanova rovnováha K+: Na+: INTRA EXTRA RT [ion]o Eion = ------ ln --------- zF [ion]i [ion]o Eion = 61mV log --------- [ion]i RT PK[K+ ]o + PNa[Na+ ]o + PCl[Cl- ]i Er = -- ln --------------------------------- F PK[K+ ]i + PNa[Na+ ]i + PCl[Cl- ]o Rovnovážný potenciál – pro daný iont Nernstova r. Goldmanova r. Hnací síla = Driving Force -90mV – (Rovnovážný potenciál) Na/K ATPáza – „nabíjí“ membránu Ouabain Jen 6 kationtů vně navíc na pozadí 220.000/220.000 nabije membránu Klidový potenciKlidový potenciááll UloUložženenáá energie pro generovenergie pro generováánníí,, šíšířřeneníí aa zpracovzpracováánníí elektrických signelektrických signáállůů:: AkAkččnníí potencipotenciááll –– vhodný pro dvhodný pro dáálkový,lkový, nezkreslený a rychlý pnezkreslený a rychlý přřenos signenos signáállůů MMíístnstníí potencipotenciááll –– vhodný pro zpracovvhodný pro zpracováánníí,, syntsyntéézu, modifikaci informaczu, modifikaci informacíí AkAkččnníí potencipotenciááll http://www.http://www.hhmihhmi..orgorg//biointeractivebiointeractive//vlabsvlabs//neuneu rophysiologyrophysiology/index./index.htmlhtml Jak se dnes měří a jak vypadá? The Nobel Prize in Physiology or Medicine 1963 "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane" Sir John Carew Eccles Alan Lloyd Hodgkin Andrew Fielding Huxley 1/3 of the prize 1/3 of the prize 1/3 of the prize Australia United Kingdom United Kingdom Australian National University Canberra, Australia University of Cambridge Cambridge, United Kingdom London University London, United Kingdomb. 1903 d. 1997 b. 1914 d. 1998 b. 1917 Hodkgkin & Huxley napěťový zámek, 1963. Dodávaný proud kompenzuje iontové toky tak, aby napětí zůstalo konstantní. Proud je registrován. Na – TTX (Tetrodotoxin) – „ucpe“ ústí kanálu K – TEA (Tetraethyl amonium) Čtverzubec Tetraodon - fugu http://www.osel.cz/index.php?clanek=238 Propagace, Voltage clamp http://bcs.whfreeman.com/thelifewire/content/chp44/4402s.swf K čemu ještě voltage clamp? Otevírají se Na nebo zavírají K kanály? Zamknutí membrány vyšachuje napěťově sensitivní kanály a iontové toky jsou důsledkem jen mechanické manipulace! Různé proudy přes membránu po pohy bech cilií u různých hodnot „zamknutého“ napětí. Není to ani K ani jen Na, jsou to neselektivně kationty. KanKanáály aly a patchpatch clampclamp Kanály – prostředek udržování integrity buňky a komunikace Kanály – typy vrátkování Ionotropní transdukce – receptor přímo na kanálu Metabotropní transdukce Už jste se potkali s kanály? Řídí předávání signálů nesených ionty. Struktura – Transmembránové proteiny Rekonstrukce podle vlastností 4 domény, 6 segmentů Refrakterní fáze kanálu – omezení frekvence AP Citlivý na napCitlivý na napěěttíí SelektivnSelektivníí SchopnýSchopný inaktivaceinaktivace Na kanál Citlivý na napCitlivý na napěěttíí Na kanál a citlivost na napětí SelektivnSelektivníí Selektivita K+ kanálu Streptomyces X-ray crystallography SchopnýSchopný inaktivaceinaktivace SchopnýSchopný inaktivaceinaktivace The Nobel Prize in Physiology or Medicine 1991 "for their discoveries concerning the function of single ion channels in cells" Erwin Neher Bert Sakmann 1/2 of the prize 1/2 of the prize Federal Republic of Germany Federal Republic of Germany Max-Planck-Institut für Biophysikalische Chemie Goettingen, Federal Republic of Germany Max-Planck-Institut für medizinische Forschung Heidelberg, Federal Republic of Germany b. 1944 b. 1942 Patch Clamp – Technika, která „vidí“ kanály při práci Neher & Sackman Terčíkový zámek, 1991 Animace patch clamp The Nobel Prize in Chemistry 2003 "for discoveries concerning channels in cell membranes" "for the discovery of water channels" "for structural and mechanistic studies of ion channels" Peter Agre Roderick MacKinnon 1/2 of the prize 1/2 of the prize USA USA Johns Hopkins University School of Medicine Baltimore, MD, USA Rockefeller University New York, NY, USA; Howard Hughes Medical Institute b. 1949 b. 1956 Roderick MacKinnon, M.D., a visiting researcher at the U.S. Department of Energy's Brookhaven National Laboratory, is a recipient of the 2003 Nobel Prize in Chemistry 'for structural and mechanistic studies of ion channels.‚ His research explains "how a class of proteins helps to generate nerve impulses – the electrical activity that underlies all movement, sensation, and perhaps even thought. The work leading to the prize was done primarily at the Cornell High Energy Synchrotron Source [CHESS] and the National Synchrotron Light Source [NSLS] at Brookhaven. The proteins, called ion channels, are tiny pores that stud the surface of all of our cells. These channels allow the passage of potassium, calcium, sodium, and chloride molecules called ions. Rapid-fire opening and closing of these channels releases ions, moving electrical impulses from the brain in a wave to their destination in the body."1 "Potassium channels act as both gateways and gatekeepers on cell membranes, controlling the flow of ions and enabling brains to think, muscles to move, and hearts to beat. Malfunctioning ion channels contribute to epilepsy, arrhythmia, and other diseases."2 Roderick MacKinnon and Ion Channels Možnosti mol. genetiky Vápníková komunikace a Ca kanály Ca v myokardu Akční potenciál kanály Propagace, Voltage clamp Akční potenciál cartoon Leukocyty, stejnLeukocyty, stejněě jako rakovinovjako rakovinovéé bubuňňkyky majmajíí napnapěťěťovověě vrvráátkovantkovanéé kankanáályly