Ion basis of electrical signaling - chapter 2

how do neurones communicate?

• Neurons behave by two types of signals: electrical or chemical signals

threshold potential

• certian level of membrane potential where action potential occurs

Electrical signals

Electricity travels through axon terminal and releases neuro transmitters which dendrites of other neuron sense

• control movement and more

Luigi Galvani

• 1797

• Exp: Accidentally electrically stimulated a frog leg and the frog leg kicked

• Discovered: Electrical current can activate muscle

• Galvanize = to shock or excite

• Discovered bioelectricity by showing that nerves and muscles generate electrical signals

Edward Hitzig and Gustav Fritsch

• 1879

• Discovered: stimulation of cortex can move limbs

• Discovered localized motor function with their experiments in dogs.

Wilder Penfield

• Exp: doing awake Surgery on pt with epilepsy

• Discovered: Stimulation of cortex can evoke memories or laughter

• Mapped the human cortex through electrical stimulation and produced homunculus

Why do we use electricity for signalling?

• Bc electricity is fast and speed is needed

  • For ex. If you are walking and your foot steps on a pin if your brain doesn’t get the signal to move your foot right away you may get severely injured. But since electricity is fast your brain gets signals fast and you can avoid/minimize injury

why are squids fast and useful to scientists?

• Squid are fast bc the neurons innervating their jet propulsion muscles have very large axons

• Squids giant axon is a LOT bigger than a mammalian axon

  • This is useful to scientist bc big things are easier to handle experimentally

  • Squid giant axon is easily accessible

two conditions for each membrane of cells

1) There are different ion concentrations across the membranes

2) membranes are selectively permeable to some ions

beaker example for electrochemical equilibrium (first part - just normal beaker with normal partition)

• Imagine you have beaker with a solid divider (vertical) that partitions it into two departments. On the left side their is very high concentrated potassium chloride and right side there is a less concentrated solution(less potassium and chloride ions) of potassium chloride. Voltage difference between two sides is 0.

  • This is bc within each side, and negative charges are equally balanced. No net charge on either side, so the difference between the sides = 0

beaker example for electrochemical equilibrium (second part - just normal beaker with broken partition)

Now if the divide had holes permeable only to potassium ions (K+). This would cause K+ ions to move down their concentration gradient causing some K+ ions on left side to move to right side. So then we have more negative charge on left side since more K+ ions moved to right.

beaker example for electrochemical equilibrium (third part - just normal beaker with broken partition

• Overtime the positive potassium ions will start being attracted to negative charge on the left side causing them to flow towards the left side. Eventually the electrical force will counterbalance concentration force. So concentration gradient is towards right and electromotive force is towards left causing them to balance each other out over time.

  • This is bc no net flow of ion in either direction. Electrical force and chemical diffusion force are equally balanced.

  • Once at the point of equilibrium: V(L-R) = negative —> potassium's equilibrium potential (Ek)

Voltage difference between left and right at potassium equilibrium potential will be negative when at equilibrium

electrochemical equilibrium

exact balance between two opposing forces

• concentration gradient and opposing electrical gradient

purpose of cell membrane

• prevents the flow of ions (semi-permeable membrane)

• acts as a divider

• Membrane acts as an insulator - does not allow electrical current to flow across

  • Hydrophobic phospholipid bilayer prevent movement if ions

[K+] for cell membrane

• High [K+] in the intracellular space

• Low [K+] out in extracellular space

ion channels

• allow for selective membrane permeability

• Allow for passive diffusion of ions down their concentration gradient

  • proteins that allow only certain kinds of ions to cross the membrane in the direction of their concentration gradients

which of the following statements accurately describes electrochemical equilibrium for potassium?

a)The point at which the concentration of potassium is exactly the same inside and outside the neuron

b) The point at which the net charge is exactly the same inside and outside the neuron

c) The point at which the diffusion force created by potassium’s concentration gradient is exactly balanced by an electromotive force in the opposite direction

C) The point at which the diffusion force created by potassium’s concentration gradient is exactly balanced by an electromotive force in the opposite direction

equilibrium potential

electrical potential generated across the membrane at electrochemical equilibrium (potential difference between outside and inside compartments)

Nernst equation

used to calculate equilibrium potential for individual ions

electric potential overcoming concentration gradient

• concentration gradient or the way the ions move can be affected by the electric potential (if making something more negative/positive)

potassium valence?

+1

chloride valence

-1

sodium valence

+1

• Nernst equation example

  • Potassium concentration (mM) Intracellular - 400 and Extracellular is 20

TopHat: If the concentration of chloride (Cl-) is greater inside the cell compared to outside the cell, will it’s equilibrium potential be positive, negative or zero?

positive because both terms negative

ion pumps

establish and maintain concentration gradients (sets equilibrium potential for each ion) -> REQUIRES ENERGY

Active transporters

• type of ion pump

  • maintain ion concentration gradients across plasma membrane

• not passive diffusion so uses energy typically in form of ATP (not always though)

  • actively move ions into or out of cells against their concentration gradient

active transporters and ion channels relationship

channels and transporters work against each other generating the resting membrane potential, action potentials, and the synaptic potentials and receptor potentials that trigger action potentials

Sodium-potassion pump

For every three sodium ions pumped outside cell, 2 potassium ions are pumped inside the cell

what works to maintain resting membrane potential?

Channels and transporters work against each other to maintain RMP

In vitro intracellular recording - how it works

• Extracted brain from organism and kept brain alive and sliced brain and put slice on dish and zoomed in using microscope to look at neuron

• To measure electrical signals of neurons take a glass pipette (recording electrode) and stab it into the neuron (intracellular space)

• Another glass pipette is stabbed in the bath solution (reference electrode)

• They both go through an amplifier so we can measure difference inside and outside of cells

  • RMP is (inside-outside)

Resting membrane potential (RMP)

The difference in voltage between the inside and outside of the cell at rest

what is typical RMP?

RMP -> Typically -65

INSIDE MORE NEGATIVELY CHARGED THAN OUTSIDE OF CELL

Using an in vitro intracellular recording approach, how would you determine whether sodium contributes to the resting membrane potential?

• Record RMP by changing or removing sodium concentration in bath and see how it affects RMP

  • RMP doesn't or barely changes so sodium doesn’t really contribute to RMP (or very very little)

    • This is bc membrane is (essentially) impermeable to sodium at rest and therefore doesn’t really contribute to the resting membrane potential

How do you determine which ions are responsible for resting membrane potential?

• Did same thing as above for potassium.

  • Found that as extracellular potassium concentration increased RMP increased which shows potassium plays a very big role in setting RMP

    • Membrane is very permeable to potassium at rest

Goldman equation

• equation that takes into account concentration gradients of permanent ions and permeability to membrane

  • since potential is also dependent on how permeable the membrane is to different ions

  • calculates resting membrane potential of cell

why is chloride the opposite in goldman equation

• Chlorides is opposite bc chloride has negative valence

Ohm’s Law

Ohm’s Law: I = V/R

• I = current

• V = voltage

• R = resistance

Ohm’s Law: I = V*G

• G = conductance

calculating conductance?

• G = 1/R

  • G = conductance

  • Conductance is essentially membrane permeability

Neurons are relatively impermeable to sodium at rest. If you could suddenly open a bunch of sodium ion channels, allowing sodium to flow freely across the membrane, what would happen to the sodium resistance and conductance immediately after you open the channels?

a) the resistance increases and the conductance decreases

b)The resistance decreases and the conductance increases

c) the resistance and the conductance both increase

d)The resistance and the conductance both decrease

b) the resistance decreases and the conductance increases

Goldman equation - imagine a membrane thats impermeable to Na+ and Cl-

• becomes Nernst equation

Ion - relative conductance - equilibrium potential (mV)    [need to memorize values]

• Vm = -65mv which also shows how potassium plays largest role in RMP(most permeable to potassium) and sodium smallest

  • relative conductance - how permeable the membrane is to that ion

  • Equilibrium potential - the membrane voltage where that ion would be in balance

RMP recap

• Active transporters establish and maintain concentration gradients

• Ion channels allow ions to passively diffuse down concentration gradient

• Number of ion channels in membrane sets conductance for that ion

• Together, ion conductances and concentration gradients control the resting membrane potential

• The neuron is a battery, storing potential energy (in the form of chemical concentration gradients) for later use

action potential role

• action potential is an electrical signal that travels along axons and briefly abolishes the negative resting potential and makes the transmembrane potential positive.

• are responsible for long range transmission of information within the nervous system

• Use stored energy to generate action potentials

• (aka spike, or impulse)

how do neurons encode and transmit information

• Neurons encode and transmit information via transient changes in the membrane potential

  • Changes in membrane potential can differ in their sign, temporal dynamics, and trigger

hyperpolarization - in terms of ___ and what happens

• Negative membrane deflections

• If current delivered makes membrane potential more negative (hyperpolarization) -> nothing dramatic happens, membrane potential just changes in proportion to magnitude of injected current  (called passive electrical responses)

depolarization - in terms of ___ and what happens

• Positive membrane deflections

• If current delivered makes membrane potential more positive (depolarization) -> once reach threshold potential an action potential occurs

action potentials - how they occur

Action potentials are all-or-none (either occurs or it doesn’t) — threshold voltage

what does a large positive current injection cause

• Beyond threshold, larger current injections will not elicit larger depolarizations. They’ll instead elicit more action potentials not “greater” action potentials

• You inject a neuron with 1.5 nA of current,. The neuron responds by eliciting an action potential. When you inject 2 nA of current, will the amplitude of the action potential increase, decrease, or stay the same?

• stays the same bc more current j produces more action potentials

how are action potentials generated?

• Generated by selective changes in the permeability of the neuronal membrane

  • At rest (~ −70 mV):

    • gK>gNa (The membrane is much more permeable to K⁺ than Na⁺)

    • more K+ inside cell than outside due to ion transporters

      • why resting potential is negative

    • Therefore:

    Vm≈EK​

    Because potassium dominates, the membrane potential sits near the potassium equilibrium potential.

• Depolarization (Rising phase)

  • gNa increases because the sodium channels opened and sodium rushes in

    • more sodium outside a neuron than inside because of ion pumps(higher concentration outside than inside)

  • transient increase in Na+ permeability → membrane potential becomes more positive

  • gNa> gK

So now:

Vm≈ENa

Because sodium conductance dominates, the membrane potential moves toward Eₙₐ (around +60 mV).

That’s why the voltage shoots upward.

This is the steep rising phase of the action potential.

• Peak of Action Potential

  At the top:

  • gNa≫gKg_{Na} \gg g_KgNa​≫gK​

  • VmV_mVm​ is close to ENaE_{Na}ENa​

  It doesn’t quite reach +60 mV because:

  • Sodium channels begin inactivating

  • Potassium channels begin opening

• Repolarization (Falling phase)

  The graph says:

  sodium channels close (gNa decreases)

  Now:

  • Na⁺ channels inactivate

  • K⁺ channels are open

  • gK≫gNa

  So:

  Vm≈EK

  The membrane potential moves back toward the potassium equilibrium potential.

• Hyperpolarization (Undershoot)

  K⁺ channels stay open briefly.

  Because:

  • gK still high (even higher than rest causing undershoot)

  The membrane potential goes even closer to (or slightly past) EK.

  This causes the small dip below resting potential.

action potential generation steps (short)

1. neuron at RMP (about -65 mV)

2. some stimulus depolarizes neuron (-55 mV)

3. Voltage gated sodium channels open allowing sodium ions to flow inside the cell

4. At peak voltage gated Na+ channels close and voltage-gated potassium channels open causing K+ to rush out of the cell, bringing the membrane potential back down towards negative.

5. Hyperpolarization (Undershoot): K+ channels stay open a bit too long, causing the membrane potential to briefly become more negative than the resting potential (below -70 mV)

6. Return to Resting State: K+ channels close, and the [sodium-potassium pump] restores the original resting ion concentrations.

how is membrane potential determined and action potential in terms of conductance

The membrane potential is determined by which ion has the highest conductance at that moment. (more permeable?)

• If gK dominates → Vm≈EK​

• If gNa​ dominates → Vm≈ENa

The action potential is essentially a shift in conductance dominance:

• K⁺ dominates at rest

• Na⁺ dominates during the spike

• K⁺ dominates again during repolarization

Why use action potentials? Why isn't passive just enough?

• If you record current at different locations on axon as you move further and further from stimulation site response decreases. This is because current leaks out of cell over time. - so only really works for shortest axons (1mm or less)

• Current can “leak” out of membrane which can be a problem bc how can brain control arms and legs

  • Loss becomes significant after only about 1-2 mml

• The way our systems solve that is through action potentials in order to maintain signals? Across long distances 

  • Basically keeps message intact

  • an action potential of constant amplitude is observed along the entire length of the axoncircumvents inherent leakiness of neurons

passive signaling

• Small current input -> membrane potential below threshold -> passive response

active signaling

• Large current input -> membrane potential above threshold -> action potential (active response)

receptor potentials

due to activation of sensory neurons by external stimuli such as light, sound, or heat (usually resulting in transient changes i the resting membrane potential)

types of neuronal electrical signals (electric signalling)

• receptor potentials

• synaptic potential

• action potential

synaptic potentials

• communication between neurons at synaptic contacts

• activation of synapses generates synaptic potentials which allow transmission of information from one neuron to another

hyperpolarization

membrane potential becomes more negative

depolarization

membrane potentials becomes more positive than resting potential

passive electrical responses

a change in a neuron’s membrane potential that occurs without opening voltage-gated ion channels and without generating an action potential.

how does the current used to evoke an action potential affect the amplitude of it.

• it does not; action potentials are all or none

• however, it can affect the number of action potentials that fire

  • intensity of a stimulus us encoded in the frequency of action potentials not their amplitude

action potential vs synaptic and receptor potential

amplitudes for synaptic and receptor potential are impacted based on sensory stimulus and number of synapses activated

anesthesia and electrical signals

• work by interfering with electrical signalling mechanisms of neurons

• blocks action potential propogation

relative conductance - potassium

1

relative conductance - Cl

0.2

relative conductance - Na

0.02

equilibrium potential (mV) - potassium

-75

equilibrium potential (mV) - chloride

-33

equilibrium potential (mV) - sodium

+55

resting potential ion concentrations

• much more K+ inside the neuron than outside

• much more Na+ outside the neuron than inside

Alan Hodgkin and Andrew Huxley

• In 1949 conducted experiment on living squid giant axon to see how RMP was affected when changing the external K+ concentration

  • as external K+ increased, the resting membrane potential becomes less negative

  • when external K+ = inside K+ → K+ equilibrium potential was 0 mV → RMP was 0 mV

• Overall showed that resting neuron most permeable to K+ than any other ion (Na+ and Cl- influence but A LOT LESS);

• more K+ inside than outside

• lowering external Na+ concentration reduces the rate of rise of the action potential and its peak amplitude but very little effect on RMP