2. Lectures 4 and 5 Rachel A. Kaplan and Elbert Heng 2.11.14

3. Announcements In case you weren’t here last time, Rachel’s email address is not rachel_kaplan@brown.edu but instead rakaplan@brown.edu rachel_kaplan@brown.edu rakaplan@brown.edu Exam 1 is in 2 weeks!

4. LECTURE 4: RESTING MEMBRANE POTENTIAL

5. Introduction Membrane Hypothesis on the RMP –Arises from high resting selective permeability to K+ and a concentration gradient for K+ ions across the membrane. Changes in K+ should change RMP

6. Giant Squid Axons An experimental tool that helped Hodgkin and Huxley to figure out relationships between ion concentrations and the membrane potential - like testing the Nernst equation –found that predicted Vm did not match their measured Vm at low concentrations of K+ –this was because the axon is not just permeable to K+ but also other ions! therefore, the membrane hypothesis isn't wholly right, but it's a pretty good guess for ye olde science

7. A Model Cell Requires us to make following assumptions –Must be electroneutral (equal - and + charges). – Osmotically balanced. –No net movement of ions. There is no ATPase

8. What determines the equilibrium potential? Determined by the two opposing forces: Electric gradient – (like charges repel, opposites attract) Concentration gradient – (too much of one ion doesn’t like to stay in one place if it has more room to go somewhere else)

9. Nernst Equation This is exactly what the Nernst equation is considering.

10. So how do equilibrium potentials determine membrane potential? If your membrane is only permeable to one ion, you’re in the clear. –Vm = Eion But usually, it’s not. –So use the GHK Equation, which takes into account relative permeabilites of ions and their equilibrium potentials to determine overall Vm. NB: Make sure to flip Cl! - Z causes reverse ratio in ln(Cl-)

12. What’s everyone’s job, and what does GHK help us determine? Na+ : Brings membrane potential more positive than Eion of K+ –But because membrane is not as permeable to Na as it is to K+, it does not contribute as much as K does. K+ : Heavy weight determinant of membrane potential –Permeability of K+ is highest of all ions, so Vm will be closest to Eion of K+

13. What’s everyone’s job? Cl- : Stabilizes the membrane potential –This is due to shunting effect – complicated, don’t ask too much about it… Na+/K+ Pump: Establishes concentration gradients –Because it exchanges more positive ions out than in (3Na+ out / 2K+ in), excess of negative charge builds on intracellular side of membrane, and subtracts 5 mV from the RMP. electrogenic

14. Membranes as Circuits

15. Membranes can be modeled as an electrical circuits –Resistors: ion channels –Battery: membrane potential –Capacitors: membrane