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Last Lecture! Tuesday (Today) : 1. One more talk by student 2. “Finish up” Nerves Brief Review of Course Probably not have time today: Will give a special session—completely optional. Time/date TBA. . Announcements. HW # 10 assigned already Covers diffusion & Nerves

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Announcements

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  1. Last Lecture! Tuesday (Today) : 1. One more talk by student 2. “Finish up” Nerves Brief Review of Course Probably not have time today: Will give a special session—completely optional. Time/date TBA. Announcements HW #10 assigned already Covers diffusion & Nerves Due Wed 12/11, 5 pm, Rm 365 LLP. Final exam: Dec 18th, 7-10pm, Here, 1304 Siebel Formally covers everything, but aside from some fundamentals, particularly covers Lec 13 (Oct 8th) – end HW # 6-10. i.e., after Mid-term exam, Oct 10th) Final written Report Due 7pm Dec 18th, at start of exam.

  2. Today: Nerves, Ion Channels 1. Ion channels are the bases of nerves. 2. They are digital—all or nothing on/off. 3. Boltzmann's factor determines probability of on/off.

  3. Action Potential– Nerves Firing http://www.biologymad.com/NervousSystem/nerveimpulses.htm

  4. Is the Ion Channel Digital or Analog?

  5. Nerve Impulse propagate, not spread, because Na+ spontaneously shut-off.

  6. Single Ion Channel Conductance Midpoint Potential: -80 mV; Steepness of curve: qV Suggests model where 2 states that differ in energy by qV Where q is about 13e, or 13e/4 per S1-S4 sub-unit; V= -80mV. q is part of channel—gating current, not ionic current!

  7. Charged amino acids (largely in the voltage sensor) move.

  8. Ion Channel Structure Schematic diagram of an ion channel. 1 - channel domains (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. http://en.wikipedia.org/wiki/Ion_channel

  9. K+ S5 S3 S6 S4 S2 S1 Outside K+ K+ K+ -0.1 V Closed Open How does gate turn on/shut off? S4 has lots of charge Feels effect of external ions 0 mV Low K+ (High Na+) S4—gate S1-S4: switch that feels voltage High K+ (Low Na+) 0 V + + + + + + There is some charged amino acids, which feels the force of voltage. Likely a rotation.

  10. Study of Fruit Flies (Drosophila) Mutant: Shaker Gene: Potassium ion channels Mutation causes change in conductance when given ether, legs shake (hence the name) Even un-anaesthetized, weird movement., repetitive firing due to neurotransmitters; requires less sleep. In Drosophila, the shaker gene is located on the X chromosome. The closest human homolog is KCNA3.

  11. 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 FRET and Crystallography But how S4 (and S1-S3) move, remain controversial. Rod MacKinnon won Nobel Prize

  12. Notice Selectivity Filter (GYG)

  13. Inside Outside

  14. Not presented in lecture

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

  16. 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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