Lecture 7 Outline Flashcards
Electrochemical gradients are dependent on both…
concentration & charge
- under physiological conditions, electrochemical gradients are established for K+, Na+ & Cl-
Membrane potential vs RMP
MP of a cell: due to electrical gradient across a cell membrane - unequal distribution of charges (ions) - established by ATPase transporters measured in mV (millivolts) not constant: - MP can change due to movement of ions
RMP
- special case of MP, where there is steady-state balance b/t active transport & leakage of ions
- for most cells, RMP b/t -20mV & -90mV
Define Depolarization
more +
- towards 0
Define Hyperpolarization
even more -
- even more away from 0
Define repolarization
more -
- away from 0
Equilibrium potential definition
the membrane potential that exactly opposes the steady state electrochemical gradient for an ion
follows the convention: “inside with respect to outside”
Nernst equation
Eion=61/z x log ([ion]out/[ion]in)
Example normal physiological conditions for equilibrium potential
K+ -90mV
Na+ +60mV
Ca2+ +122mV
Cl- -81mV
Independence
The equilibrium potential for each ion is independent of the concentration of the other ions
- ex: the equilibrium potential for K+ has NO EFFECT on the equilibrium potential for Na+ or Cl-
RMP Goldman Equation
RMP (in mV) = 61 log (Pk [K+]out + PNa [Na+]out + PCl [Cl-]in/ Pk [K+]in + PNa [Na+]in + PCl[Cl-]out)
predicts RMP considering 2 factors:
- relative permeability of Na+, K+, & Cl-
- the concentrations inside & outside the cell
Example normal physiological conditions of RMP
Normal, healthy is -78mV RMP
*the ion that has the greatest permeability contributes the most towards determining what the RMP will be
Example kidney failure Equilibrium potential
elevated [K+out]
hyperkalemic (10 mM K+)
= -67mV (depolarization)
High Na+ permeability
PNa=10 000
RMP = +58mV (VERY positive)
What would cause this?
the opening of VG Na+ channels for ex
Movement of ions changes MP: K+
relative concentration inside: high
EP = -90mV
direction of movement when ion channels out: OUT
Movement of ions changes MP: Na+
relative concentration inside: low
EP = +60mV
direction of movement when ion channels out: IN
Movement of ions changes MP: Ca2+
relative concentration inside: low
EP = +122mV
direction of movement when ion channels out: IN
Movement of ions changes MP: Cl-
relative concentration inside: low
EP = -81mV
direction of movement when ion channels out: IN
Why is the cell membrane an effective insulator?
it is able to keep charges separated from each other
Define electrochemical gradient
combo of an electrical gradient & chemical gradient
- ions subjected to an electrochemical gradient will move
Define electrical gradient
ex: inside the cell there is more (-) & outside more (+)
Define chemical gradient
ex: more of the green (-)’s inside than outside
- vice versa with the red (+)’s
Describe how to measure MP
convention is “inside with respect to outside”
Ex: if a cell has a RMP of -70 mV it is -70mv “inside with respect to outside”
- take a sharp electrode & poke it inside the neurons & measure the MP “inside with respect to outside”
Describe the hypothetical cell with a K+ pump (Active transport) and leakage channels
concentration of K+ maintained over time
system is at STEADY STATE where the rate of leakage thru leakage channels is exactly balanced by active transport
NOT equilibrium b/c it requires constant energy
Now imagine that the K+ pump (active transport) in the hypothetical cell is stopped (add a poison for ex)
K+ would eventually leak out until inside & outside are at an equilibrium
How can we make K+ stay inside if we’ve shut off the pump in the hypothetical cell?
- make inside (-)ly charged to attract K+ ions (ADD (-) charges)
- we say: “Make the inside (-) with respect to the outside”
- the amount of voltage necessary to keep the K+ inside is called the equilibrium potential, or reversal potential
What are the equilibrium potentials of key ions at physiological concentrations?
K+ -90mV
Na+ +60mV
Ca2+ +122mV
Cl- -81mV
If only one ion was permeant, RMP would be…
the equilibrium potential for that ion
ex: if K+ was the only permeant ion, RMP would be -90 mV
however all real cells are permeable to Cl, K+ & Na+ (they’re leaky b/c they have leakage channels…)
so we need an equation to account for leaky ions & their electrochemical gradient
What is the relative permeability for Na+, K+, Cl- and anions- (proteins, etc)
Na+ 1
K+ 50
Cl- 10
Anions 0
Why isn’t Ca2+ in the Goldman Equation (even though there is a difference inside & out for Ca2+)?
b/c in a resting cell, Ca2+ is virtually impermeable (NO leakage channels for calcium) so that is why Ca2+ would drop out of this equation
if Ca2+ DIDN’T drop out of this equation it would be about 2 pages to write the whole thing out b/c Ca2+ has a valence of 2
so Ca2+ drops out to:
- simplify the math
- the resting permeability is 0
Why is Cl- flipped for the Goldman Equation?
b/c Cl- is a (-)ly charged ion
What does it mean that K+ has the HIGHEST permeability (50 compared to 1 for Na+ & 10 for Cl-)?
that means that K+ has the MOST INFLUENCE on where the RMP is gonna go
- therefore, the RMP will tend TOWARDS the equilibrium potential for K+
- so changes on K+ ion concentrations will have the biggest effects on RMP
What happens if only 1 ion is permeant in the Goldman equation?
the RMP will be the equilibrium potential for that ion
Ex: if PNa & PCl- (permeability) went to 0, then they will all become 0 & the RMP will be K+ equilibrium
*so the ion that has the greatest permeability contributes the most towards determining what the RMP will be
Movement of ions at physiological concentrations depends on what 2 factors?
- Equilibrium potential &
2. MP of the cell
When ion channels open:
the ion always moves to make MP = Equilibrium potential
Describe what will happen in this physiological condition:
RMP = -78mV Ena = +60mV
to make RMP more (+)/closer to +60mV you have to bring more (+)ly charged ions INTO the cell
Describe what will happen in this physiological condition: (ADULT NEURONS Cl- low inside cell)
RMP = -78mV Ecl- = -80mV
Cl- ions will move IN to make the MP more like the EP
Describe what will happen in this physiological condition: Cl- transporter protein (KCC2) not present (EARLY brain development, & epilepsy)
RMP = -78mV Ecl- = -50mV
- EVEN THOUGH there is more (-) outside than inside, Cl- will move OUTside to make the RMP more like the EP
- therefore, doesn’t really follow the concentration gradient
- ions don’t always move according to the simple concentration gradient, but they move according to their electrochemical gradient & you can figure out which way they will move when you consider that “the ion always moves to make MP = EP
