lecture 3- excitability pt 1

Question 1

define excitability

Answer 1

the generation & conduction of electrical charge by specialized cells in human body

Question 2

nerves and impulses are ___ cells, can display property of generating and conducting ___

Answer 2

excitable
electrical impulses

Question 3

define excitable membranes

Answer 3

electrical impulse generated at surface of membrane of excitable cells and travels along membrane

Question 4

excitable membranes share 2 electrical properties:

Answer 4

capacitance & conductance

Question 5

___ is the ability of membrane to separate electrical charge one side from the other (positive charge on one side and neg charge on the other)

Answer 5

capacitance

Question 6

___ is the ability of membrane to transport or move charge one side to the other

Answer 6

conductance

Question 7

every nerve impulse is an ___

Answer 7

electrical current

Question 8

name a few charged ions in solution

Answer 8

Na+
K+
Ca2+
Mg2+
Cl-
HCO3-
Pro-

electrical charge- contributes to electrical nature of membranes

Question 9

describe the distribution of ions across typical nerve cell in mammalian body

Answer 9

sodium higher outside than inside, charge unequally separated across membrane

potassium higher inside than outside, charge unequally distributed across membrane

chlorine higher outside than inside

individual ions and charges separated

(entire total charge- can only tell if membrane has net charge on one side or the other if you measure it)

Question 10

describe how you measure charge on a membrane

Answer 10

potentiometer (specific voltmeter)- 2 electrodes, put one on outside and one through membrane on inside of cell

• reference electrode sets its side of the membrane to zero
• recording electrode (sticks through membrane to inside) measures the difference in electrical charge b/w reference and recording electrode (inside & outside of membrane)

Question 11

the inside of the membrane has a net negative charge relative to the outside

what is it? what is it called?

Answer 11

-70 mV

this charge on the membrane called:
potential difference
TMP (transmembrane potential)
resting potential

Question 12

when you measure the transmembrane potential, how does it differ between nerve cell types?

Answer 12

it is fairly constant (-70 mV) on all nerve cell types –> so it is called resting potential (RP)- electrical charge on a nerve cell at rest, not active

Question 13

where does the -70 charge exist in a nerve cell?

Answer 13

only at the inside surface of membrane

• relative pos charge only exists on outside surface of membrane at interstitial fluid
• if a fluid is large enough to be measured, going to be relatively neutral (surface of membrane is its own compartment, inside and outside of cell are neutral)

Question 14

the membrane has the property of ___, unequal distribution of charge - pos on outside and neg on inside

Answer 14

polarity

Question 15

excitable membrane generates this -70 mV charge by a combination of…

Answer 15

capacitance and conductance

Question 16

name 3 factors that govern ion movement

Answer 16

concentration gradient
relative speed due to permeability
electrical gradient

Question 17

describe scenario #1 with beaker of water divided in half (6 Na+ & 6 Cl- on side a)

Answer 17

concentration gradient determines direction– ions begin moving to side b

• have to measure relative permeabilities (the more permeable ion will move faster)- chloride more permeable than sodium, Cl- will diffuse faster
• at an intermediate stage, side a is more positive & side b is more negative because more Cl- has moved

–> sodium will catch up at completion, diffuse until reach equilibrium, no concentration or charge difference across membrane

IF ACTING BY SIMPLE DIFFUSION ALONE, REACHES EQUILIBRIUM, IONS MOVE BACK & FORTH RANDOMLY

Question 18

real nerve cells are not at equilibrium, must be something more than simple diffusion…

compare distribution of protein at membrane

Answer 18

proteins concentrated high inside the cell, not outside

at physiological pH, protein has a net negative charge

Question 19

describe scenario #2 with beaker of water

side a: 6 Na+ 6 proteins-
side b: 6 Na+ 6 Cl-

Answer 19

sodium already at equilibrium- no net movement
- protein is very large so net permeability is virtually zero (protein does not diffuse, stays at side a)
- Cl- has large concentration gradient (6:0), so will diffuse from side b to a

intermediate stages: some Cl- has moved to side a (net negative charge at side a and net positive charge at side b)
- so concentration gradient favors movement of Cl- to side a (however Cl is negative and side a is negative so charge is repelled)
–> interaction of 2 opposing forces- conc gradient pushes Cl- from side b to a BUT electrical gradient pushes Cl from side a to side b

• in many cases, concentration gradient and electrical gradient work in opposite directions
• in many cases, electrical gradient may be strong enough to hold an ion outside of equilibrium with respect to its concentration

so in this situation, electrical gradient holds chloride out of equilibrium (2 on side a & 4 on side b)
- opposite for sodium- electrical gradient pulls sodium outside of equil, but conc gradient strong enough to prevent electrical gradient from pulling Na across

Gibbs- Donnan equilibrium

Question 20

what is Gibbs-Donnan equilibrium

Answer 20

equilibrium established between two forces (concentration and electrical gradient)

• exists when unequal distribution of large impermeable negatively charged ion- (in almost all cases, that is unequal distribution of protein)
• result of Gibbs-Donnan is unequal distribution of permeable particles across membrane

Question 21

does Gibbs-Donnan explain resting potential of membrane

Answer 21

no

Question 22

what 2 forces often work in opposite directions across membranes

Answer 22

concentration and electrical gradient

Question 23

describe scenario #3 with water beaker but put charge across membrane by putting battery and electrodes in solution

equal amounts of sodium & chloride on both sides, side a is positively charged, side b neg

Answer 23

side a is pos charged, side b is neg charged

• start with equal amounts of chlorine and sodium on both sides…electrical gradient creates concentration gradient
• b/c side b is negative, electrical gradient pulls sodium to side b, concentration gradient then wants to pull sodium back to side a because less Na+ now on side a
• same with chlorine, electrical gradient pulls chlorine to side a b/c side a is positive, conc gradient wants to pull Cl- back to side b b/c less there
• at equilibrium, unequal concentration and charges (but have equilibrium b/w concentration gradient and electrical gradient)- conc gradient pushes ions downhill and electrical gradient works to pull them back

Question 24

how do concentration and electrical gradient even out?

Answer 24

there is a strength of concentration gradient that will equal out the strength of the electrical gradient and vice versa

Question 25

describe the equations that are derived to form Nernst equation

Answer 25

work done by electrical gradient = work done by concentration gradient W(elec) = zFE z = charge on ion F = faraday constant E = actual electrical charge on membrane W(conc) = 2.303 RT log ((ion)in/(ion)out)) T= temp R= universal gas constant **solve for E (E is called equilibrium potential) this says --> for every ion concentration gradient, there is a charge on the membrane that is equal and opposite in strength

Question 26

state the nernst equation

Answer 26

E = (-60 mV log [ion]in / [ion]out) / z

Question 27

use the nernst equation to figure out if chloride is in equilibrium b/w its conc and elec gradients determine: value of equilibrium potential in equilibrium or not transport mechanism [Cl-] out: 120 mM [Cl-] in: 10 mM

Answer 27

E = log(10/120) x -60 / -1 E = -64.75 the farther away from zero, the greater the charge on the membrane (more polarity), larger the potential --> -70 mV is greater potential than -65, so resting potential is high enough to hold it in place - chloride ion in equilibrium b/w its concentration and electrical gradients - transport mechanism: simple diffusion

Question 28

describe the 2 transport mechanisms of ions depending on the ions equilibrium potential

Answer 28

if ion is in equilibrium --> simple diffusion if ion is out of equilibrium --> active transport

Question 29

use nernst equation to figure out if potassium is in equilibrium b/w its conc and elec gradients [K+] out: 5 mM [K+] in: 150 mM

Answer 29

E = log (150/5) x -60 / +1 E = -88.6 equilibrium potential of K+ is larger than resting potential (-89 > -70), so K ions are not in equilibrium transport mechanism: active transport to maintain concentration gradient

Question 30

use nernst equation to figure out of sodium is in equilibrium b/w its conc and elec gradient [Na+] out: 150 mM [Na+] in: 15 mM

Answer 30

concentration gradient favors movement of Na+ inward...electrical gradient also favors movement of Na+ inward b/c inside is negative (-70)...but concentration of sodium is still way higher outside, why??? E = log (15/150) x -60 / +1 E = +60 way out of equilibrium transport mechanism: active transport

Question 31

the sodium pump is also called ___ and is a large ___ protein

Answer 31

Na/K dependent ATPase transmembrane

Question 32

where does the energy of the sodium pump come from

Answer 32

energy comes from domain inside membrane having ATPase activity (sodium pump has ATPase, ATPase only active when both sodium and potassium in its presence) Na/K dependent

Question 33

describe the sodium pump mechanism

Answer 33

inside membrane, 3 binding sites for sodium (3 sodiums bind inside membrane), this allows an ATP to bind to active site and be split, releasing stored energy of the higher phosphate ATP bond --> this changes the protein configuration, pushes 3 sodiums across membrane and release them outside --> new shape allows 2 potassiums to bind, changes shape a bit, causes phosphate group to be knocked off, protein goes back to normal shape and releases potassium inside

Question 34

result of the sodium pump when finished

Answer 34

3 sodium out & 2 potassium in - each time, takes 1 ATP to do that - establishes the Na+ and K+ gradients to begin with, active transport

Question 35

brief overview of sodium and potassium channels

Answer 35

since the ions are charged, have to go through channels that are specific for the individual ion itself (Na+ channels only allows Na+ through, same with K+) - these channels are not just holes in the membrane, they are like doors that open and close --> when sodium channel open, said to be "activated," when closed- "deactivated" or "gated" - potassium channels swing back & forth, when open, lets it pass through, when closed, doesn't

Question 36

sodium and potassium channels are called ___ channels

Answer 36

voltage-gated channels voltage/charge determines whether channel is open or closed

Question 37

what are Na+ and K+ channels like at rest (-70 mV)

Answer 37

at rest (-70 mV), most sodium and potassium channels are closed

Question 38

why are potassium and sodium channels so specific and how do they allow ion transfer to go through?

Answer 38

specificity filter allows ion and its associated hydration shell to fit very snugly in the channel as ion moves through, the hydration shell is ion is stripped off and the negative charges on the oxygens of the amino acids that line that channel substitute the hydration shells and the neg charges keep the ion in solution and keep it moving through as sodium ion leaves, reacquires hydration shell- when out of channel, fully rehydrated

Question 39

active transport of sodium pump transports ions across membrane and establishes ___

Answer 39

concentration gradients

Question 40

once conc gradients are established from sodium pump, what happens?

Answer 40

the tendency of ions is to diffuse back down concentration gradients...but they do not diffuse at the same rates - the channels restrict the ions differently --> K+ channels allow K+ to diffuse faster b/c of higher permeability & Na+ channels restrict Na+ movement, lower permeability - for every 30 K+ ions that diffuse outward, only 1 Na+ ion diffuses inward (for every 30 pos charges that diffuse out, only 1 positive charge diffuses back in) --> net negative charge inside - when reach a steady state, left with -70 mV inside, this is how resting potential is established (stored potential energy which will be released in action potential)

Question 41

relate conductance and capacitance to sodium pump and ion channels

Answer 41

conductance- action of the sodium pump moving positive charged potassium in and sodium out capacitance- separates charge by differential permeability -- positive charge diffuses out faster than positive charge diffuses inward (leaves inside neg)