Lecture 5 - Neuro 2, Ion movement

Resting membrane potential (RMP)

• -70 mV

• Actively maintained, dynamic equilibrium; Net flux =0, so equal ion movement in and out

Factors that contribute

• Distribution of ions near plasma membrane

  • More (+) on outside, more (-) inside - especially large, impermeable anions

• Na/K Pump

  • 3 Na out, 2 K in (will make inside more negative)

  • Direct effect - between -2 and -5 mV

  • Indirect effect - maintains ionic gradients by active transport, drives current through leaky channels

• Leaky channels - Predominant determinant of RMP

*Active transport maintains concentration gradients in resting neurons

Leaky channels

• Leaky channels - Somewhat constitutively active (on most of the time, though always open as a population)

  • K+ will flow out (down electrochemical gradient towards Equilibrium potential, which is more negative)

    • Inside of cell becomes more negative as K+ leaves, and stops once K+ reaches Eq (net flux K+ = 0)

  • Na+ will leak into the cell (more positive Equilibrium potential)

• After action potential, Na/K pump moves 3 Na+ out and 2 K+ in (net negative)

  • Na/K pump - small contribution to returning to RMP; it most importantly maintains the gradients in concentration that allows the flow through leaky channels

AP Steps in terms of Gates

1. Resting membrane potential (before AP)

• Vm ≈ −70 mV

• Voltage-gated Na⁺ channels: CLOSED

• Voltage-gated K⁺ channels: CLOSED

• Leak channels: OPEN

📌 Only leak channels matter here

2. Depolarization (rising phase)

• A stimulus depolarizes the membrane to threshold (~ −55 mV)

👉 Voltage-gated Na⁺ channels OPEN

• Fast opening

• Na⁺ rushes in

• Membrane rapidly depolarizes toward ENa+

📌 This is when voltage-gated channels are clearly open

3. Peak of action potential

• Vm ≈ +30 mV

• Voltage-gated Na⁺ channels INACTIVATE

  • Not just closed — inactivated

• Voltage-gated K⁺ channels BEGIN to open

📌 Na⁺ influx stops, K⁺ efflux starts

4. Repolarization (falling phase)

• Voltage-gated K⁺ channels OPEN

• K⁺ flows out

• Vm becomes more negative

📌 This is the second time voltage-gated channels are open (K⁺ now)

5. After-hyperpolarization

• K⁺ channels close slowly

• Vm becomes more negative than RMP

6. Return to resting membrane potential

• Voltage-gated K⁺ channels finally CLOSE

• Voltage-gated Na⁺ channels reset from inactivated → closed

• Only leak channels remain open

📌 Leak channels now dominate and pull Vm back to RMP

*Na/K Pump is kinda always working, but its impact is small on the action potential

Impact of K+’s high permeability

• Makes the Vm / RMP very negative

  • For Depolarization - Gives Na+ a very big driving force, making the membrane explosively depolarize when Na+ voltage-gated channels open

• For Repolarization - Because the Vm is +30 and the EK+ is ~ -90 Vm, K+’s driving force is huge when it leaves the cell

• For the Refractory period - Na+ channels inactivated, K+ channels close slowly while the membrane still is highly permeable to K+ → causes the Vm to become more negative than RMP, closer to K’s Eq

  • Neuron returns to RMP through the leaky channels

Goldman Equation - calculate Equilibrium potential

• Resting membrane potential approaches (but doesn’t reach) EqK+

  • PM is highly permeable to K+, which is why the RMP is so close to K+’s Eq, but the presence of the more positive Eq molecules → **Na+ and Cl- (a little) → make the RMP slightly more positive

How do membranes become more permeable for firing action potentials?

• Opening / closing ion channels

• **Movement of a small number of ions alters the membrane potential ; this amount is too small to alter the concentration gradient

  • Ion concentrations don’t meaningfully change

• Membrane potential is about charge separation, not total ions

  • Vm arises from:

    • Slight excess of + charge on one side

    • Slight excess of − charge on the other

  • One action potential changes ~1 in 10⁶ Na⁺ or K⁺ ions, and concentration gradients remain essentially unchanged

  • That’s why neurons can fire thousands of APs without “running out” of ions

    • **Na/K Pump is still needed since small leaks can add up, so it restores the gradients slowly, preventing long-tern drift

Changes in potential relative to RMP

• Depolarization - Vm becomes less negative

  • + ions enter, or -ions exit

• Hyper polarization - Vm becomes more negative

  • +ions exit, or -ions enter

• Repolarization - Vm returns to RMP

  • 2 types:

    • During the downward of Action Potential : getting. more negative, so ions exit, or -ions enter

    • After Hyperpolarization: getting more positive, so + ions enter, or -ions exit

Driving force

• Difference between Vm and Eq of an ion

• Determines the rate of ion flow

• Bigger driving force = faster rate

  • Not constant, depends on current Vm

    • Big DF = sharper slope

    • Little DF = flatter slope

Neuron signal reception

• Dendrites

• Could be:

  • Neurotransmitters

  • Sensory stimulus (for a sensory neuron)

• Signal transformed from a chemical to a membrane potential

• Signal reception leads to graded potentials

Graded potentials

• Signal reception → graded potentials

  • Graded potentials are the stimulus that triggers action potentials when they summate and depolarize the Vm to -55mV

• Occur in dendrites and somas

• Caused by ligand-gated ion channels (and mechanically gated channels)

• Characteristics:

  • Vary in magnitude and duration, proportional to the strength of the stimulus

  • Transient, occur locally

  • Short distance signals - can degrade over a large area

  • Can be excitatory or inhibitory

• Graded potentials can ad up at the axon hillock (spatial summation - from different synapses, & temporal summation - same rapid stimulus over time)

Ligand-gated channels cause Graded Potentials

• Channel opening is proportional to amount of ligand present

  • Ligand concentration varies continuously

    • Ligand concentration (neurotransmitter) depends on stimulus strength ; stronger stimulus = more ligand

  • Channel opening probability varies continuously

  • Ion flow varies continuously

• Therefore, the voltage change:

  • Can be small or large

  • Depends on stimulus strength

  That’s the definition of a graded potential.

Graded potentials decay over short distances

• Positive ion enters

  • Repels other + ions, attracts - ions; Electrical signal spreads over a very short distance, decays

• Electrotonic - passive current due to electrical interactions within the cell

• Electrotonic spread can be described by length constant 𝜆