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1843

curare. Direct stimulations on Nerves----impulse Direct stimulations on Muscles----contraction. Curare +. Curare + stimulation on nerves → muscles’ contraction. X. 1843. Claude Bernard (France) Physiologist

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1843

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  1. curare Direct stimulations on Nerves----impulse Direct stimulations on Muscles----contraction Curare + Curare + stimulation on nerves → muscles’ contraction X 1843 Claude Bernard(France) Physiologist Interested in mechanism by which nerves stimulate the contraction of skeletal muscles →Curare somehow acted on the region of contact between the nerve and muscle

  2. 1843→1906 John Langley Physiologist in Cambridge Uni. Study the ability of nicotine to stimulate the contraction of muscles and the effect of curare in inhibiting nicotine action →Impulse should not pass from nerve to muscle by an electric discharge, but by the secretion of a special substance on the end of nerve. “Chemical transmitter” and “receptive substance”

  3. 1843→1906→1921 Otto Loewi Physiologist (Austrian-born) Stimulate the nerve and then transfer the solution to a new heart without vagus, the new heart is inhibited as its own inhibitory nerve have been activated. →Vagusstoff is acetylcholine(Ach)

  4. 1843→1906→1921→1937 DavidNachmansohn Neurophysiologist at the Sorbonne Electric organs of ray are derived from modified skeletal muscle tissue which is rich of acetylcholinesterase (AChase) and nicotinic acetylcholine receptor (nAChR).

  5. Suitable assay to determine the protein Chen-YuanLee and his colleagues National Taiwan Uni. 1963 α-Bungarotoxin in the venom of a Taiwanese snake

  6. 1843→1906→1921→1937→1970s Isolation of nAChR Electric organs containing the nAChR Blend Homogenate containing the nAChR Centrifuge Pellet contains membranes fragments Triton X-100 Affinity chromatography Purified nAChR

  7. Affinity chromatography

  8. 1843→1906→1921→1937→1970s Structure of nAChR ArthurKarlin (Columbia Uni.) nAChR is a pentamer. It contains 2 copies of α subunit ,and one copy each of β, γ, and Δsubunit. 4 different subunits are homologous to one another, each subunit containing 4 homologous transmembrane helices.

  9. 1843→1906→1921→1937→1970s Structure of nAChR Jean-PierreChangeux (Pasteur Institute) The receptor acts as both a site for binding ACh and a channel for the passage of cations. The binding of ACh to the receptor caused a conformational change that opened an ion channel within the protein.

  10. Sequencing, mutation Electron microscope Methods 1843→1906→1921→1937→1970s→pasttwo decades Structure of nAChR

  11. 1843→1906→1921→1937→1970s→pasttwo decades Detailed model of nAChR Nigel Unwin and his colleagues (Medical Research Council of England)

  12. The sequence of events during synaptic transmission with Ach as the neurotransmitter

  13. Thanks for your listening

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