PNB 2264 - Unit 6

Neurophysiology

Excitability

=membrane potential; basis of field of electrophysiology

Attractive forces only work over a __ distance.

short

If we want to keep opposite forces separate, it takes a lot of __ to do so.

energy investment

Why are membranes semipermeable?

-plasma membrane is responsible for keeping charged particles separate from one another

-plasma membrane must compartmentalize ions and keep them at different concentrations on either side of the membrane (interstitial fluid has a different ion concentration than the cytosol)

-ions can't freely pass the membrane (selective)

The plasma membrane can regulate the movement of ions (charged particles) and it can do that using _ __ ___ such as ion channels and transporters.

Integral membrane proteins

2 principles of membrane semi-permeability

1. Intact membranes do not allow ions to pass freely (separation of charge)

2. Ion channels and carriers permit the movement of ions across the membrane (change concentration gradient)

Membrane potential

-the uneven distribution of electrical charge across the membrane

-the movement of ions creates changes in membrane potential

-basis of muscle contraction and nervous communication observed by Galvani

-the potential energy to do work

What does a negative voltage tell you about a cell?

The inside of the cell close to the membrane is more negative than the outside

Vm is the potential the cell relative to the potential _ the cell. It is expressed as a voltage.

inside; outside

How do cells create membrane potential?

-The plasma membrane is able to create compartmentalization, which allows us to have different concentrations of ions on either side.

Distribution of Important Ions (4)

4 biologically important ions: K+, Na+, Cl-, Ca2+

Interstitial fluid = ?

Cytosol = ?

Extracellular

Intracellular

Key contributions to Vm

1. Ions are not distributed equally across the cell membrane (unequal concentrations)

2. Membranes are unequally permeable to various ions (different permeability)

Without permeability, membrane potential _ exist because ions cannot move.

CAN'T

Diffusion

Ions will move from high concentration to low concentration so long as the concentration gradient exists

When the distributions of ions is equal on both sides of the membrane, does a concentration gradient still exist?

NO because the net charge cancels out

ex. net charge in intracellular and extracellular environment: 4 + and 4 - , so (+4) + (-4) = 0

If we don't have any difference in charge across the membrane, then the membrane potential is _.

ZERO

Importance of selective permeability

-If we had freely permeable membranes and ions could just move down their concentration gradients entirely, we would eventually end up with equal concentrations of those ions on both sides of the membrane

-Everything would be completely balanced and that means membrane potential would not exist and excitable tissues like nerves and muscle would not function properly

Attractive forces

-Attractive forces between charged particles kick in and influence the movement of ions

-Opposites attract, so some ions (depending on which ones the membrane is permeable to) will be pulled back into or out of the cell (depending on where the attractive force exists) because of this electrostatic force

Electrostatic force

-There is electrostatic attraction between negative charges in (or out) the cell and positive charges out of (or in) the cell

-The repulsive forces acting on like charges (- and - or + and +) are attempting to push them away from the environment

Note. some ions can't move in or out of the cell b/c of the selectively permeable plasma membrane, so either the attractive or repulsive force will overpower the other.

Forces that set membrane potential

1. Concentration gradient (pushing ions towards chemical equilibrium).

CONCENTRATION = CHEMICAL

2. Electrical potential (pushing ions towards electrostatic equilibrium).

ELECTRICAL = ELECTROSTATIC

Vm is a balancing act between which two opposing forces?

concentration gradient AND electrical potential

when those two forces balance each other equal and opposite, what we end up with is MEMBRANE POTENTIAL.

Equilibrium potential (Ex)

-the voltage that an ion would create across the membrane if we were to allow those two forces to be balanced until they were equal and opposite, and that net flux of that ion across the membrane would be ZERO

-the balancing point between concentration gradient and electrical potential is different for every single ion, so every ion has a unique Ex

Ions experience the effects of two different forces:

1. a chemical driving force that is due to their concentration gradient

2. an electrical driving force that is due to charge-charge interactions (electrical potential)

The equilibrium potential for an ion, Ex, is the membrane potential at which the _ ___ and _____ _ forces are EQUAL and OPPOSITE.

concentration gradient; electrical potential

At E(K), K+ is at ____. There is _____ net flux of ion K+ across the membrane.

equilibrium; no

How are cells in the body like the ocean?

-The relative concentrations of ions almost NEVER change under normal circumstances inside your body, even when channels are open (unless in disease state or lab).

-When ions do move, they can create big changes in voltage BUT they don't create changes in voltage for the ENTIRE cell. They only change the voltage at the PLASMA MEMBRANE (right where the "food coloring" is dropped). That is the place where the ions are coming into or moving out of through channels.

-Why it's called membrane potential and not cell potential

Despite movement of ions, relative concentrations of ions __ change.

DO NOT.

Small movements produce big changes in Vm.

3 parts to equilibrium potential

The voltage that would develop across the membrane if an ion was allowed to move until its (1) concentration gradient and its (2) electrostatic forces were balanced until they were equal and opposite, AND the (3) net flux of the ion was zero (steady state)

The equilibrium potential for an ion is determined by _ and ____ _____ (not constants).

charge; concentration gradients

Why is it difficult to change equilibrium potentials?

The only things that affect Ex are charge and concentrations gradients, which are factors that cannot be easily manipulated. You would need a nuclear reactor to change the charge, and homeostasis generally prevents major shifts in ion concentrations, which is why Ex remains the same for ions under normal circumstances.

Why is the Ex for potassium negative?

K+ has a higher concentration inside the cell than outside, so it diffuses down its concentration gradient from a high to low concentration. Therefore, K+ must move from inside the cell (high) to outside the cell (low). Because the inside of the cell is LOSING positive charge, it is becoming more negative, which is why it has a negative Ex.

Why is the Ex for sodium positive?

Na+ has a higher concentration outside the cell than inside, so it diffuses down its concentration gradient from a high to low concentration. Therefore, Na+ must move from outside the cell (high) to inside the cell (low). Because the inside of the cell is GAINING positive charge, it is becoming more positive, which is why it has a positive Ex.

Why is the Ex for chloride negative?

Cl- has a higher concentration outside the cell than inside, so it diffuses down its concentration gradient from a high to low concentration. Therefore, Cl- must move from outside the cell (high) to inside the cell (low). Because the inside of the cell is GAINING negative charge, it is becoming more negative, which is why it has a negative Ex.

T/F: Equilibrium potential does not equal membrane potential.

TRUE.

-Our cells are never permeable to just one ion (like Ex assumes). We have K+, Na+, and Cl- permeability all going on at the exact same time.

-Therefore, the Nernst equation cannot be used to calculate membrane potential because it only takes into account one ion.

Resting Membrane Potential (Vm)

-steady state (does NOT = equilibrium)

-point where the net flux of an ion is zero

-condition where all the ions that are moving have equal and opposite movements to each other, net flux is zero

-voltage that develops across the membrane from the movement of all permeable ions

Membrane potential and permeability

You can move from the resting membrane potential by changing ion permeability

Relationship between equilibrium potential and membrane potential

-different but related concepts

-equilibrium potentials help to determine membrane potential

-membrane potential is a WEIGHTED average of equilibrium potentials. The weight is the permeability of that ion, which varies for each ion.

Resting membrane potential is a _ average of the Ex for each ion, if a cell is permeable to multiple ions.

weighted; permeable

Electro-chemical tug of war

-Balancing act between the concentration gradient and electrostatic forces

-Ex is the voltage that each ion wants the membrane to be at

-All of the ions are pulling at the exact same time (they're trying to pull membrane potential towards its own Ex)

Membrane potential can never be more than the most positive Ex and more _ than the most negative Ex.

positive; negative

E(Na) is most positive -- ceiling

E(K) is most negative -- floor

How does permeability influence membrane potential?

-Vm must fall between the largest Ex (+58mV) and smallest Ex (-75mV)

-the strength of the "pull" is determined by the ions permeability (more permeable ions are able to move the membrane potential closer to their Ex, less permeable ions don't have much of an influence on membrane potential b/c they're too weak)

Why is the resting membrane potential -70mV?

Because potassium has the highest permeability and thus pulls the membrane potential closest to its equilibrium potential, which is -75mV.

Leaky potassium channels

-one family of potassium channels that are open at rest

-reason for potassium's high permeability

-potassium is high inside, so efflux makes resting Vm negative

When would membrane potential equal equilibrium potential?

If we're only permeable to one ion and the permeability for all the other ions is zero, the GHK equation reduces down to the Nernst equation.

2 ways to change membrane potential

1. change concentration gradients for ions (difficult to do)

2. change permeability of an ion (easy to do b/c every cell has a whole complement of ion channels that it can open or close)

Plasma membrane

allows for ions to be unequally distributed

Ion channels

allow membranes to be unequally permeable

Why are concentration gradients critical?

-ion channels are passive transport (no energy, rely on diffusion, high to low concentrations)

-if all we did was move ions from high to low concentrations, then there wouldn't be any concentration gradient anymore and membrane potential would be zero

-so, active transporters (ATPase pump) helps prevent this from happening and ensures that concentration gradients always exist

Sodium-potassium pump

-the ATP that the pump consumes allows it to pump both sodium and potassium against their concentration gradients (actively)

-3Na+ get pumped out, 2K+ get pumped in

-this guarantees that the concentration of Na+ inside the cell is always going to be kept low and concentration of K+ is always going to be kept high inside the cell