Lecture-04-2011-Bi-CNS150

Lecture-04-2011-Bi-CNS150 - Henry Lesters office hours Mon,...

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1 Bi/CNS 150 Lecture 4 Monday, October 3, 2011 Presynaptic transmitter release Henry Lester’s “office” hours Mon, 1:15-2 PM, Fri 1:15-2 outside the Red Door Chapters 11, 14
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2 Proof of chemical synaptic transmission, 1921 Vagus nerve runs from the head to the heart Spontaneous heartbeats in both hearts are stopped by stimuli to the “upstream” vagus smoked drum The diffusible substance: acetylcholine acting on muscarinic ACh receptors
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[neurotransmitter] open closed chemical transmission at synapses: electric field open closed electrical transmission in axons: Past lectures: V-gated Na + channels V-gated K + channels Today: V-gated Ca 2+ channels 3 Wednesday: ACh-gated excitatory cation (Na + / K + / Ca 2+ ) channels & GABA- and glycine-gated inhibitory anion (Cl - channels Next week: Glutamate-gated excitatory (Na + / K + / Ca 2+ ) channels
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4 Many basic principles of chemical transmission were discovered at the neuromuscular junction (nerve-muscle synapse); acetylcholine is the transmitter. Figure 11-1
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0.3 µm Fine structure of the NMJ Figure 11-1 From Lecture 4 5 ACh receptors Incl. acetylcholinesterase
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Life cycle of a synaptic vesicle Caught by flash-freezing, invented at Caltech ~ 50 yr ago A. Van Harreveld Presynaptic terminal postsynaptic cell
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Proteins in synaptic vesicle membranes slide 1 A. Homogenize brain in isotonic sucrose. B. Isolate synaptosomes B. (cut-off nerve terminals) by differential and sucrose gradient centrifugation C. Lyse synaptosomes in hypotonic solution to release vesicles. D. Isolate vesicles by glass bead column chromatography. Vesicles can be isolated from brain tissue by cell biological methods
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Synaptophysin Synaptotagmin (the Ca 2+ sensor) Snares (residents of either the vesicle [v-snare] or the target membrane [t-snare]) VAMP (also called synaptobrevin), a v-snare Syntaxin, a t-snare that also associates with Ca 2+ channels (technically not a vesicle protein) SNAP-25, a t-snare (~25 kD; also technically not a vesicle protein) ATP-driven proton pump creates concentration gradient that drives neurotransmitter uptake against concentration gradient (one of three transporters that function in transmitter release) Proteins in synaptic vesicle membranes, slide 2 Mary Kennedy’s work Lecture 1 asked, “Could cells utilize plasma membrane H + fluxes?” “Probably not. There are not enough protons to make a bulk flow, required for robustly
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This note was uploaded on 01/03/2012 for the course BI 150 taught by Professor Kennedy,m during the Fall '08 term at Caltech.

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Lecture-04-2011-Bi-CNS150 - Henry Lesters office hours Mon,...

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