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Homework #8 assigned today 4/19/10, due next Wednesday . Wednesday, 4/21/10: Quiz on reading from ECB, Nerves.

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  1. Homework #8 assigned today 4/19/10, due next Wednesday. Wednesday, 4/21/10: Quiz on reading from ECB, Nerves. This Friday, 4/23/10: email your final topic verbal and oral presentation. Include both a write-up and PDF of the research paper. It must be on a totally different topic (technique and biology) than mid-term presentation. I will get back to you by Monday 4/26/10. Announcements Final Paper: due evening May 5th. Final presentation—need two days (3 meetings): Monday May 3rd, Wednesday May 5th, night of Wednesday May 5th, 5pm (Pizza included.) Final Lectures: W, April 21st; M April 26th; W April 28th

  2. Quiz (Chpt 12, ECB) 1. Membrane transport proteins can be divided into two main classes:___________ and ___________. The basic difference between these two classes of membrane transport proteins is the way they___________________ _______. transporters channels discriminate between solutes 2. In passive transport, an uncharged solute or an ion is transported ___________its electrochemical gradient. In active transport, an uncharged solute or an ion is transported __________it concentration or electrochemical gradient in a process that requires _______________. down against energy 3.Solute transfer carried out by transporters can be ______________; transport by channels is _________________. active or passive always passive 4. The Na+-K+ pump in the plasma membrane of animal cells is _____________ that actively transports Na+ _______of the cell and K+ ______. an ATPase in out action 5. Neurons propagate signals in the form of ______ _____________, which are usually mediated by voltage-gated ________________ that open in response to ______________of the plasma membrane potentials Na+ channels depolarization 6. Different types of stimuli influence the opening and closing of ion channels. List three classes of gated ion channels that are controlled by different stimuli: _________ ____________, ______________ and ________________. voltage- ligand-gated gated stress-activated (Mechanosensitive)

  3. how many different ion channels? Ans:25-30,000 genes: 5000-6,000 genes. One or more polypeptide/ion channel– could get less, or more, ion channels.

  4. Ion Channels 0 mV 0 mV (open, depolarized) -60 to -100 mV (closed, polarized)

  5. Shaker Potassium Ion Channels

  6. Start of Action Potential I said Ca2+ released, e.g. by muscle. But nerve propulsion also starts by sodium inflow, largely with mechanosensitive receptors. In skin cells, mechanically-gated sodium channels. The Pacinian Corpuscle Proprioception is our "body sense". --pressure, vibration receptors, located in skin, and various internal organs (joints, tendons and tissues that lines the organs and blood vessels), connected to a sensory neuron. They are the largest of the skin's receptors and are believed to provide instant information about how and where we move. http://www.biologymad.com/NervousSystem/nerveimpulses.htm

  7. K+ S5 S3 S6 S4 S2 S1 Potassium & Sodium Channel Similar K+ Channel: homotetramer S1-S6 Na+ Channel heterotetramer S1-S6: with each sub-unit havingslight variations) Bezanilla, 2008, Nature Reviews

  8. K+ S5 S3 S6 S4 S2 S1 X-ray Crystal Structure

  9. Structure of Pore-Domain(S5-S6) is known(KvAP, Kv1.2… all yield the same structure) Explains ion selectivity (K+ > Na+) and rapid ion flux.Excellent agreement between LRET/FRET and Crystallography But how S4 (and S1-S3) move, remain controversial. Rod MacKinnon won Nobel Prize

  10. Notice Selectivity Filter (GYG)

  11. Hydration Energy If 10,000 fold selectivity, what is ENavs. EK ? Ans: 9.2kT Sodium channel been crystallized. C=O just right for Na+.

  12. Inside Outside

  13. Point mutation in Potassium Gene that affects Potassium Channel

  14. K+ S5 S3 S6 S4 S2 S1 Outside K+ K+ K+ -0.1 V Closed Open How does gate turn on/shut off? 0 mV Low K+ (High Na+) High K+ (Low Na+) 0 V + + + + + +

  15. Roderick MacKinnon S4 S4 Jiang et al. Nature, 2003 Resting How does gate (S4) move? General Models Rotation? Piston? Paddle? Cork-screw? Blaustein and Miller, Nature427, 499-500. (2004). Crevice Reshaping?

  16. LRET using stationary toxins MacKinnon Model Only 2Å change! Not much change Not translation model. We believe rotation model.

  17. Class evaluation • What was the most interesting thing you learned in class today? • 2. What are you confused about? • 3. Related to today’s subject, what would you like to know more about? • 4. Any helpful comments. Answer, and turn in at the end of class.

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