26 September 2011 Lab this week: Four Endocrine Cases –Bring textbook –Optional: Bring laptop with AirTerrier Test # 1 =Monday, Oct 3 rd. –Test Material Cutoff to be announced Friday. Lab next week: Measuring action potential conduction velocity in human ulnar nerve.

1QQ # 9 for 8:30 class 1.A) List the four categories of glia cells of the central nervous system and B) state which category you would choose to eliminate from your CNS if you were forced to do so, being sure to C) give your reasons for your selection. 2.A) Describe the location and purpose of a growth cone and B) how axonal transport is associated with growth cones.

1QQ # 9 for 9:30 class 1.A) List the four categories of glia cells of the central nervous system and B) state which category you would choose to eliminate from your CNS if you were forced to do so, being sure to C) give your reasons for your selection. 2.A) Describe the location and purpose of a growth cone and B) how axonal transport is associated with growth cones.

Virtues of Squid Giant Axon Big questions: 1)How do cells generate a resting membrane potential? 2)What causes changes in the membrane potential? 3)How do cells use these potentials? i.e. What is their purpose?

Fig

Fig a There is a concentration gradient favoring the diffusion of Na+ and K+ through the selectively permeable membrane which has ion channels only for potassium. At the start, is there an electrical driving force?

Fig b With K+ channels open, K+ diffuses down its concentraiton gradient, leaving behind CL- ions which are not permeable through the membrane. As more and more K+ move to the left, the compartment they leave becomes more and more negatively charged. Is there an electrical driving force?

Fig c

Fig d Soon, the accumulation of negative charges seriously impeded the diffusion of K+ as the electrostatic force builds up in opposition to the concentration driving force.

Fig e Equilibrium potential = Nernst potential = diffusion potential Eventually, the electrostatic force that impedes diffusion of K+ is exactly equal to the driving force favoring diffusion based on a concentration gradient. When these two driving forces are equal and opposite, the membrane potential reaches an equilibrium at which the voltage is called So which compartment corresponds to intracellular fluid? E ion+ = 61/Z log ([conc outside]/ [conc inside]) E K+ = 61/1 log (5/150) E K+ = -90 mV

The Nernst Equation If the membrane is permeable to ONLY ONE ion species and you know the concentrations on both sides of the membrane, use the Nernst Equation to calculate the membrane potential. Nernst potential for X = 61/Z log [Outside ] / [Inside] S 2

Fig e Equilibrium potential = Nernst potential = diffusion potential E ion+ = 61/Z log ([conc outside]/ [conc inside]) E K+ = 61/1 log (5/150) E K+ = -90 mV 150 mM5 mM K+ 50 mM Predict the change in membrane potential if K+ were added to the extracellular fluid. S 1 What hormone regulates the levels of Na+ and K+ in extracellular fluid?

Fig a S 3 Now consider a situation in which only Na+ is permeable.

Fig b S 4

Fig c S 5

Fig d S 6

Fig e Equilibrium potential for Na+ E Na+ = 61/1 log (145/15) E Na + = +60 mV 145 mM 15 mM Extracellular Intracellular So, given these concentrations of Na+ and a membrane permeable only to Na+, use Nernst equation to calculate what the membrane potential would be. At the equilibrium potential, no net movement of Na+ because driving forces (concentration and electrical) are exactly equal and opposite. S 7

Electrical and concentration gradient driving forces for Sodium and Potassium How does the membrane potential change if 1) permeability to sodium increases 2) Permeability to potassium increases Why is resting membrane potential closer to E K than E Na ? What would happen to membrane potential if suddenly P Na became very great? Size and Direction of Arrows show driving forces! The G-H-K Equation! S 8

The Goldman Hodgkin Katz Equation If you know the concentrations of ALL permeable ions and their relative permeabilities, you can calculate the membrane potential using the GHK Equation. S 9

At RMP, some Na+ leaks in, some K+ leaks out. S 10

Na+ K+ ATPase maintains the concentration gradients across cell membranes Animation of the Pump What would happen to membane potentials and concentrations of Na+ and K+ if cells didn’t have this pump? S 11

Animations of the Origin of Resting Membrane Potential Animation of Resting Membrane Potential (single ion) YouTube animation of Na-K-ATPase, Sodium Co-transporter, and K Leak channels Origin of Resting Membrane Potential and intracellular recording S 12

S 13

Which ion moving in which direction (into or out of cell) is responsible for depolarization and overshoot? Which ion moving in which direction (into or out of cell) is responsible for repolarization and hyperpolarization? Can the membrane potential go more negative than -90 mV? Increase PK+ Increase PNa+ S 14 Increase PK+ How do ions get across the membrane? Ion channels!

Graded potentials are conducted decrementally for only a few millimeters, die out over distance and time, and are proportional to the size of the stimulus. Leak Channels Gated Channels ….. Ligand-gated ….. Mechanically-gated ….. Voltage-gated Electrogenic Sodium- Potassium ATP-ase maintains concentrations across membrane 2K+ 3 Na+ S 15

Open Na+ channels, Na+ goes _____ Open K+ channels, K+ goes _____ S 16

Graded potentials are conducted no more than 2mm Insect bites foot (stimulus). Sensory neuron produces graded potential in proportion to intensity of the stimulus. How is signal conducted to the brain? S 17