10. The Action Potential Part 2: Ionic Permeability and Channel Conductance

What happens when you inject negative current into an axon, and how is it measured?

• Two probes are used:

  • One injects current & measures Vm

  • The other measures Vm at a distance

• Injecting negative current makes inside more negative → hyperpolarization at point A

• Removing negative current makes current leak out the cell → returns to resting membrane potential

• This shows that neurons respond to changes in ionic current by changing their membrane potential (Vm)

Why is no change in membrane potential detected at point B when injecting small current?

• The current is too small to reach threshold → no action potential

• The membrane leaks charge, so current decays before reaching point B

• Therefore, Vm at point B stays the same

What happens when you inject positive current into the axon?

• Small positive current → slight depolarization (Vm becomes less negative)

  • But decays with distance → no effect at point B

• Large positive current → reaches threshold → action potential triggered

• AP seen at both points A & B

  • Delay in time at point B due to propagation time

• Action potentials are triggered by depolarization!

How do changes in ionic conductance cause the action potential?

• During rising phase: Na+ conductance (gNa) ↑ rapidly → Na+ enters → depolarization

• At AP peak, Vm does not reach ENa (+58) because:

  1. Sodium channels close quickly after opening, they only stay open briefly

  2. Potassium channels open during the peak of the AP, allowing K+ to leave the cell

     • K+ conductance (gK) also ↑ → K+ leaves

     • Outward K+ current offsets inward Na+

Key takeaways so far

1. Action potentials require threshold depolarization to open sodium channels

2. Sodium influx drives depolarization, but potassium efflux and sodium channel closure prevent Vm from reaching ENa

3. Repolarization is due to potassium leaving the cell, bringing Vm back toward resting potential

4. The timing of channel opening and closing is critical: sodium first, potassium later

Which factors change the magnitude of ionic current across the membrane?

• Ionic current (I) depends on:

  • gion (conductance/permeability)

  • Vm - Eion (driving force)

• gion changes the most during AP

• Vm changes moderately

• Eion changes the least

• At rest:

  • PK = 1 (high)

  • PNa = 0.04 (low)

  • PCl = 0.45

• During AP → PNa increases greatly, changing current flow

Why is Vm at rest closer to EK, and what changes during an action potential?

• At rest: PNa ≪ PK → Vm close to EK

• During AP: PNa sharply increases → more Na+ enters → depolarization

• Ion permeability can change due to:

  • Voltage-gated channels opening/closing

  • Channel conformation changes triggered by Vm

How is the voltage-gated sodium channel structured and how does it relate to permeability?

• Single protein with 4 tra nsmembrane domains

• P-loops (between helices 5 & 6) form selectivity filter for Na+

• S4 helix = voltage sensor → detects changes in Vm

• Voltage change → conformational change → opens channel → increases permeability

How do Na+, Ca2+, and K+ voltage-gated channels differ?

• Na+ & Ca2+ channels: one large subunit with 4 domains

• K+ channels: 4 separate subunits form the pore

• S4 segment acts as voltage sensor in all → detects depolarization

• Depolarization → conformational change → channel opens → ions flow

How does depolarization cause ion channels to open?

• S4 region = gating charge region (positively charged)

• When the cell depolarizes:

  • Inside becomes less negative

  • Positive charges in S4 move outward

  • Causes conformational change → channel opens

How do the two Na+ channel gates work during depolarization?

• Na+ channels have:

  • m-gate (activation) → opens fast after depolarization

  • h-gate (inactivation) → closes slowly after depolarization

• At rest: m closed, h open

• After depolarization:

  • m opens immediately → Na+ enters

  • h closes later → Na+ stops entering (inactivation)

• Conductance depends on Vm because both gates are voltage-sensitive

How does Na+ entry create a positive feedback loop?

• Depolarization → ↑ PNa → Na+ enters → more depolarization

• This opens more Na+ channels → even greater depolarization

• Continues until most Na+ channels open → Vm approaches ENa

How do voltage-gated K+ channels behave during an action potential?

• Closed at rest

• Have n-gate, which opens slowly with depolarization

• Slower than Na+ m-gate → delayed K+ outflow

• n-gate opens as Na+ h-gate closes

• K+ efflux → repolarizes the cell

• n-gate closes again after hyperpolarization

How do voltage-sensitive Na+ and K+ channel gates respond to depolarization?

Channel	Gate	Response	Speed
Na+	m gate	opens	fast
Na+	h gate	closes	slow
K+	n gate	opens	slow

What is the sequence of ion channel changes during an action potential?

• Step 1: Depolarization begins

  • Na+ m-gates (activation gates) open quickly

  • → Na+ rushes into the cell → Vm becomes more positive

  • → Triggers nearby Na+ channels to open (cascade effect)

  • Vm moves toward ENa (but doesn’t reach it fully)

• Step 2: Peak of the action potential

  • Na+ h-gates (inactivation gates) start to close (slower)

  • K+ n-gates begin to open

  • → Na+ influx stops, K+ efflux increases

  • Vm now moves back toward EK → repolarization

• Step 3: Repolarization & return to rest

  • During repolarization:

    • h-gates reopen (ready for next AP)

    • n-gates close (stop K+ outflow)

  • Vm returns to resting potential (~ -70 mV)