Transcript AChR - 首都师范大学精品课程网

1843
Claude Bernard (France)
Physiologist
curare
Interested in mechanism by which nerves stimulate the
contraction of skeletal muscles
Direct stimulations on Nerves----impulse
Curare +
Direct stimulations on Muscles----contraction
Curare + stimulation on nerves →
X muscles’ contraction
→Curare somehow acted on the region of contact between
the nerve and muscle
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”
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)
1843→1906→1921→1937
David Nachmansohn
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).
Suitable assay to determine the protein
Chen-Yuan Lee and his colleagues
National Taiwan Uni.
1963
α-Bungarotoxin in the venom of a Taiwanese snake
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
Affinity chromatography
1843→1906→1921→1937→1970s
Structure of nAChR
Arthur Karlin (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.
1843→1906→1921→1937→1970s
Structure of nAChR
Jean-Pierre Changeux (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.
1843→1906→1921→1937→1970s→past two
decades
Structure of nAChR
Methods
Sequencing, mutation
Electron microscope
1843→1906→1921→1937→1970s→past two
decades
Detailed model of nAChR
Nigel Unwin and his colleagues
(Medical Research Council of England)
The sequence of events during synaptic transmission with Ach as the
neurotransmitter
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