The Acetylcholine Receptor

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EXPERIMENTAL PATHWAYS

• The Acetylcholine Receptor

Presented by Ian LEE
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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
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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
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1843?1906?1921
Otto Loewi Physiologist (Austrian-born) Stimulat
e 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)
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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).
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Suitable assay to determine the protein
Chen-Yuan Lee and his colleagues National
Taiwan Uni. 1963 a-Bungarotoxin in the venom of
a Taiwanese snake
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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
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Affinity chromatography
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1843?1906?1921?1937?1970s
Structure of nAChR Arthur Karlin (Columbia Uni.)
nAChR is a pentamer. It contains 2 copies of a
subunit ,and one copy each of ß, ?, and
?subunit. 4 different subunits are homologous to
one another, each subunit containing 4 homologous
transmembrane helices.
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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.
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1843?1906?1921?1937?1970s?past two decades
Structure of nAChR
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1843?1906?1921?1937?1970s?past two decades
Detailed model of nAChR Nigel Unwin and his
colleagues (Medical Research Council of England)
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The sequence of events during synaptic
transmission with Ach as the neurotransmitter
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Thanks for your listening