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L312/Spring 2007 Lecture 7 Drummond

L312/Spring 2007 Lecture 7 Drummond . • Today: Focus on Chapter 16, 542-557: Transmembrane signaling involving G-proteins • Next Thursday, Ch. 16 557-567. Class news: Exam is coming in 10 days! Study questions part II to be posted after the next lecture

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L312/Spring 2007 Lecture 7 Drummond

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  1. L312/Spring 2007 Lecture 7 Drummond • Today: Focus on Chapter 16, 542-557: Transmembrane signaling involving G-proteins • Next Thursday, Ch. 16 557-567. Class news: Exam is coming in 10 days! Study questions part II to be posted after the next lecture • This week’s content IS covered on first exam (but not next Tuesday). Timing for review sessions will be decided on in class Thursday and posted later Andrian will post keys starting today--my fault they haven’t gotten up Review key points: a. Considered three classes of gated ion channels: by voltage, ligand and mechanical stress b. Three conformations of voltage gated sodium channel control directional movement (closed but ready, open and sodium passes, then inactivated). c. K+ flux (leak) across a membrane without counterion (e.g. Cl-) causes a voltage (voltage = separation of charge; resting in many nerve cells ~ -60 mV) flow is “down” a concentration gradient (favorable) d. Depolarization signal (e.g. mechanical stress in hearing) causes slight rise in potential (e.g. to -40 mV) that triggers voltage gated sodium channel e. Signals are propagated directionally without loss of intensity (how?) system recovery is by Na/K exchanger (ATP driven) restoring concentration gradients f. Voltage gated Ca++ channel at nerve termini fires last, causes vesicular fusion with membrane neutrotransmitters are released, diffuse to next cell, triggers ligand gated channel g. Signals are highly integrated; many inputs for each neuron. Today: Transmitting information across membranes (signal transduction).

  2. What triggers a response in the next cell in the network? Break to review ‘movie’

  3. Small changes in voltage (more positive) are amplified by voltage gated sodium channels What happens to the membrane Potential when sodium rushes in?

  4. e.g. glutamate, acetylcholine What kinds of responses are possible at neuromuscular junctions? e.g. GABA, glycine Note how membrane potential can be modulated

  5. How can information be transmitted across a membrane (not material) e.g. glutamate, acetylcholine (excitatory; Ca++, Na+) Or glycine, GABA (gamma amino butyric acid) (inhibitory; Cl-) Focus on today Focus Thursday

  6. What happens when a signal molecule binds outside the cell (v 1.0) Membrane! Why have multiple targets? Multiple messengers?

  7. What are the hallmarks of a G-protein-linked receptor? How is the signal relayed to the inside?

  8. What are the key subunits of a G-protein? How are they linked To the plasma membrane? What is the physical benefit of linking to the membrane? What are the crucial intra- cellular changes that occur upon ligand binding?

  9. How does dissociation of the G-protein lead to intracellular changes? Note: this is a cycle! What happens to the Inactive G-protein?

  10. How is the G-protein cycle like other signaling* pathways *any cellular response that is Modified by information input

  11. In class discussion exercise: • Imagine an international emergency--aliens invading from Mars! • Only one phone is working on campus • The POTUS is going to call us with instructions • Power is out everywhere • The University president is in his residence awaiting instructions • A series of emergency action plans have been pre-agreed upon by the police • a. Evacuate campus to Bedford • b. Send all students into housing • c. Get all students to scream outside (in case Martians hate noise) • d. Turn off all lights and everyone go to Bears • e. Split into majors and try to devise ways to attack Martians • f. Trigger doomsday device and utterly destroy campus • Describe how our class might effect a response • Analyze the response--what are the key elements of a successful response?

  12. How transmembrane signaling parallel our invasion response?

  13. What are some of the ‘downstream’ outcomes after binding? Acetylcholine primarily acts As a sodium channel ligand!

  14. G-proteins mostly commonly act via a second messenger system What is the value of having the Enzyme amplifier in the membrane?

  15. cAMP is an important mediator of the original signal Close your book and Draw the structures!

  16. An example of signal amplification using serotonin and cAMP Blue = low cAMP (50 nM) Yellow = intermediate Red = high concentration (1000 nM) What gives the color? What kind of scope? Classic response: adrenaline triggers Glycogen breakdown--but many more!

  17. An extraordinary number of intracellular responses are mediated By kinases (use ATP to phosphorylate); phosphate is off/on signal

  18. Phospholipase C is another crucial early target of G-proteins What is a lipase? Why is an inositol phospholipid associated with the membrane? What does PLC do? IP3? How is the signal further amplified? Note where Ca is stored!!!

  19. Calcium influx in response to egg fertilization Where does the calcium come from? What are the clues?

  20. How transmembrane signaling parallel our invasion response?

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