MSK 2: RESTING membrane potential

What is resting membrane potential?

The difference between electric potential in the intracellular and extracellular matrices of the cell when not excited

-need potential in order to get things going; comes from charges inside and outside the cell

What are key determining factors with RMP?

Difference between intra- and extra- ion concentrations

-high concentrations Na+, Cl-, Ca++ extracellularly

-high concentrations of K+ intracellularly (most important for motor neurons!!)

Na-K pump (ATPase)

-for every 3 Na+ out, 2 K+ go in as long as ATP (energy is present)

Permeability

How do RMPs allow for voluntary and involuntary muscle contractions?

Via action potentials (APs)

No RMP = No AP

Changes in RMP → APs → cellular communication

Why is -70 mV the RMP of motor neurons?

-Why not zero, why negative?

Because you need a net difference to have potential

Negative due to net deficit because 3+ going out and only 2+ going in

What is a concentration gradient?

Each ion has its own (unaffected by others)

Na+/K+ gradients are created by Na+/K+ pump

Ions flow from high to low

At rest, most cells are mostly only permeable to K+ = K+ gradient has the greatest effect on Vm

Clinical concern: pay close attention to pt’s with conditions that cause K+ imbalances and be cautious with IV K+

What is an electrical gradient?

Attraction across membrane by unpaired charged ions

Unequal build up of ions on either side → electrical gradient

Separation of charge by ion channels → electrical gradients

Under steady state conditions, the electrical gradient for an ion will catch up with its concentration gradient and the two will reach equilibrium. What is the net movement of charges across the membrane?

0; nothing happening

Differences in concentration across membrane allows for ____

Diffusion/ Diffusion Potential

Diffusion potential causes a change in charge (electric potential) which →

allows for impulses/ muscle contraction

How do ions flow?

Ions flow along their electrochemical gradient

Neurons have open “leak” channels that allow K+ and Na+ to travel across membrane

Concentration gradient pushes K+ out via leak channels

Na/K pump expels 3 Na+ in exchange for 2 K+ → creates concentration gradients for Na and K

What ions have a higher concentration intracellularly?

K+ and anions

What ions have a higher concentration extracellularly?

Na+, Cl-

What direction does K+ flow and what is the impact it has on RMP?

K+ flows out of the cell (extracellularly) and makes the cell more negative

What direction does Na+ flow and what is the impact it has on RMP?

Na+ flows into the cell (intracellularly) and makes the cell more positive

What direction does Cl- flow and what is the impact it has on RMP?

Cl- flows into the cell (intracellularly) and makes the cell more negative

What direction do anions flow and what is the impact it has on RMP?

Anions can’t move/ don’t move out of the cell

Anions help keep the RMP negative because they sit inside the cell and don’t flow anywhere

What is Ex (equilibrium potential) for an ion?

amount charge (mV) found on inside of the membrane when net movement is zero

-membrane potential at which there is no net movement of the ion

-electrical potential difference across the cell membrane that exactly balances the concentration gradient for an ion

Amount of negative charge on inside of cell membrane when the gradients for all ions with open channels are equal is RMP (Vm)

Why is the neuron RMP so close to the Ek (equilibrium potential) of K+?

K+ is more intracellular and very permeable

If K+ is the ion with the greatest concentration inside the cell (motor neuron) and it is + charged, why is the inside of the cell negatively charged?

Because 3 Na+ leave for every 2 K+ that enter the cell (net deficit)

What happens if only K+ can cross membrane?

K+ leaks out of the cell via leaky K+ channels because Na/K pumps not working and they want to go from a higher concentration to a lower concentration, leading to a more negative inside potential (eventually hyperpolarizing)

What does the NERNST equation determine?

Looks for equilibrium potential for each individual ion based on its concentration gradient

-comparison of concentration inside the cell and concentration outside the cell

-relative concentration of an ion determines an individual ion’s equilibrium (Nernst) potential

-resting membrane potential is sum of equilibrium potentials of major ions multiplied by their membrane permeabilities

What do leaky channels use to transport ions across the membrane?

Diffusion

What do Na/K pumps use to transport ions across the membrane?

Active transport by hydrolyzing ATP

Gated channels are closed at rest. But what channels are always open?

leaky K+ channels

What factors contribute to membrane permeability?

Number of open channels

-ion channels lower resistance than the hydrophobic bilayer

-physiological factors can open/close these channels

Net driving force → push ions to diffuse (along concentration gradient)

-rate of ion movement

What physiological factors play a role in opening/closing channels?

Endocrine signals (ligand gated)

Neuromodulation (ligand and/or voltage gated)

Physical stimuli (mechanically gated); touch, pain, light

What contributes to the rate of ion movement?

1. concentration separation of a given ion (how much is inside/ how much is outside)

2. membrane potential (electrical gradients)

3. dynamic permeability of the membrane to that ion

How would the RMP of a cell be affected if there was an increased number of Na/K pumps?

Make it more negative

How would the RMP of a cell be affected if there was a downregulation of K+ leak channels?

Make it more positive

How would the RMP of a cell be affected if there was an expression of a small number of Cl- leak channels?

Make it more negative

How would the RMP of a cell be affected if there was an expression of twice as many K+ leak channels?

Make it more negative

What is depolarization?

RMP becoming more positive

Allows us to send a message/facilitate muscle contraction

What is repolarization?

The RMP becoming more negative

Like resetting RMP

Slower

What is hyperpolarization?

The process where the RMP becomes more negative than the resting membrane potential, making it less likely for the cell to generate an action potential.

Goes below our starting point (-70 mV)

How do hypernatremia, hypercalcemia, and hyperchloremia impact RMP?

They are all controlled by voltage gated channels and there’s no voltage at rest therefore they aren’t relevant at rest

What happens to RMP with hyperkalemia (increased extracellular K+)?

leaky K+ channels stop working and the cell becomes more positive, potentially leading to depolarization/ muscle contraction

What happens to RMP with hypokalemia (decreased extracellular K+)?

Na/K pumps stop working, mainly leaky K+ channels which causes the cell to become more negative, leading to hyperpolarization and potentially decreasing excitability

Membrane potential vs. Equilibrium potential

Membrane potential refers to the electrical potential difference across a cell's membrane

-potential to get back to -70 mV while looking at ALL ions

Equilibrium potential is the electrical potential that balances the concentration gradient for a specific ion

-dependent which ion we are looking at

How is RMP established and maintained?

Na+/K+ ATPase pumps

Leaky K+ pumps