what is the asymmetric distribution of ions across a membrane
- In summary:
o Na+ (intracellular < extracellular)
o K+ (intracellular > extracellular)
o Cl- (intracellular < extracellular)
o Proteins (intracellular > extracellular)
what does the asymmetric distribution of ions result in
chemical and electrical driving force
what is a membrane potential
electrical potential difference between the inside of a cell and its surroundings
Why is there an asymmetric distribution
Enables cells to maintain osmotic homeostasis; want to avoid movement of excess water into the cell causing lysis.
describe potassium diffusion across a membrane
K+ conc gradient leads to K+ efflux
K+ efflux leads to charge separation
electrical potential difference starts to drive electrodiffusive flux of K+ back into cell
electrical potential increases until electrical driving force balances chemical driving force
what is the equilibrium potential for K+
-90mv
what is the nerst equation
what determines the resting membrane potential
movement of potassium / sodium ions
Na-K ATPase
why is the conc of K higher on the inside in the first place
can be attributed to the K+ being attracted to the negatively charged proteins and fixed anions inside the cell
what mechanism does the Na⁺/K⁺ ATPase pump work via
electrogenic transport mechanism
pumps 3 Na+ out for every 2K+ in
what does the stoichiometry of the pump result in
a net loss of positive charge which contributes to the polarisation of the membrane
how does the pump work
- binds of three Na⁺ ions to high-affinity sites on the cytosolic face of the pump.
- triggers the phosphorylation of the pump via the hydrolysis of ATP
- leads to a conformational shift to the E2 state, which exposes the Na⁺ ions to the extracellular environment and facilitates their release.
- the pump’s conformational change enhances its affinity for two K⁺ ions, which bind from the extracellular space.
- induces dephosphorylation of the pump, reverting it to its original E1 conformation.
- results in the translocation of K⁺ ions into the cytoplasm.
whats more significant to RMP - pump or channels
channels
pump only contributes to about 2-5 mV
rest is channels
describe the movement of ions to form the RMP - leakage
- Intracellular K+ > extracellular K+, so chemical diffusion of K+ is out
- This means the outside of the membrane becomes more positive and the inside is more negative so K+ diffuses electrically into the cell
- Diffusion occurs until chemical = electrical gradient, and the equilibrium potential for potassium when this happens is -90mV
- Extracellular Na+ > intracellular Na+, so chemical diffusion of Na+ is in
- Makes the membrane potential less negative (Ena = +58mV)
- Extracellular Cl- > intracellular Cl-, so Cl- diffuses in
- Resting membrane potential = -75mV (closer to Ek than Ena, since at rest the membrane is more permeable to K+ than Na+).
Em is the balance of Ek, Ena and Ecl (it is the value for which there is no net charge across the membrane)
why does Ek not equal Em
assumes single-ion permeability.
In reality, cellular membranes are permeable to multiple ions = each exerting its own electrochemical gradient
what is the constant field equation / goldman equation
what does the goldman equation show
- Shows that the greater the membrane permeability to a particular ion, the greater impact that ion will have on the membrane potential
- The overall membrane potential is a compromise between all the equilibrium potentials of the different ions as all the ions act to drive the membrane potential towards their specific equilibrium potential.
- However, the ion to which the membrane is most permeable, has the greatest influence and thus the membrane potential is closest to their equilibrium potential.
what is one assumption of the goldman equation
is that the electrical field is constant across the membrane
simplification works well when considering the bulk of tissue but may not hold true in nanoscopic spaces, such as those found in the brain, where charge density can be spatially heterogeneous.
In these small-scale environments, variations in ion concentrations and local membrane properties can lead to significant fluctuations in the electric field, potentially impacting the resting membrane potential
What characterizes hyperkalemia?
Hyperkalemia is characterized by elevated serum potassium levels exceeding 5.0 mEq/L.
What are some causes of hyperkalemia?
Causes of hyperkalemia include renal failure, cellular shifts due to acidosis, or tissue trauma that releases potassium into the bloodstream.
How does increased extracellular potassium affect the resting membrane potential?
Increased extracellular potassium reduces the concentration gradient across the cell membrane, making the resting membrane potential less negative.
A less negative resting membrane potential decreases the threshold for depolarization, making cells more excitable.
early depolarisation + cardiac arrhythmias
How does patiromer help treat hyperkalemia?
releasing calcium ions and binding to potassium ions in the gastrointestinal tract, swapping calcium for potassium.
Patiromer is not absorbed into the bloodstream due to its large polymeric structure and high molecular weight = no passive diffusion across the intestinal epithelium.
potassium bound to patiromer in the intestines is excreted through feces, reducing the amount of potassium that enters the bloodstream.
What characterizes hypokalemia?
Hypokalemia is defined by serum potassium levels falling below 3.5 mEq/L.
What are some causes of hypokalemia?
excessive gastrointestinal losses, diuretic use, or inadequate dietary intake of potassium.
