NPB 101: Lecture 7 - Action Potential I

Learning Objectives: Describe the sequence of sodium and potassium conductance changes underlying the threshold, depolarization, peak, repolarization, and after-hyperpolarization phases of an action potential. Explain how the voltage- and time-dependent states of sodium and potassium channels produce the action-potential waveform. Distinguish the positive-feedback process responsible for rapid depolarization from the negative-feedback processes responsible for repolarization. Explain now action-potential frequency and patterns of activity across populations of neurons can encode information even through individual action potentials are all-or-none.

Sodium (Na⁺) Channel

Specialized transmembrane proteins that allow sodium ions (Na⁺) to cross cell membranes.

• Both voltage and time gated

  • Voltage-gated:

    • Inward current (Na⁺ enters the cell)

    • Responds rapidly to depolarization

    • Three states:

      • Deactivated: Closed but capable of opening

      • Activated: Open upon depolarization.

      • Inactivated: Closed and NOT capable of opening. Inactivation is caused by time-gate and is removed upon repolarization.

  • Time-gated:

    • Stops membrane from further depolarizing

    • Responds to depolarization with a slight time delay (~1 ms after activation gate opens)

    • “Ball and Chain”

      • When voltage-gate is closed, the balls float freely

      • When the gate is open, the balls are attracted to the open pore of the channel + will block the pore

      • Upon repolarization, the voltage-gate closes and the ball is dislodged, returning the Na⁺ channel to its resting closed state

Potassium (K⁺) Channel

Specialized transmembrane protein complexes that allow the selective outward flow to potassium (K⁺) ions to drive repolarization.

• Voltage gated

  • Outward current (K⁺ leaves the cell)

  • Opening and closing depends on membrane potential

  • Slow response

  • Two states:

    • Deactivated: Closed but capable of opening

    • Activated: Open around the peak of the action potential (+30mV) to let K⁺ ions flow out of the cell, returning the AP from a positive peak back down to a negative resting state

Conductance of Na⁺ and K⁺ Channels

The conductance changes with membrane potential for voltage-gated Na⁺ and K⁺ are very similar.

• When an axonal membrane is depolarized more, more of both channels will open

However, the conductance changes with time is very different for the two channels:

• Voltage-gated Na⁺ channels:

  • Opens immediately following depolarization

  • Inactivates after < 1 ms

• Voltage-gated K⁺ channels:

  • Opens after a delay (when AP reaches its peak)

  • Does NOT inactivate

Stage One of the Action Potential

Resting State (Resting Membrane Potential)

• Near E_K, P_K > P_Na due to leaky K⁺ channels

• K⁺ and Na⁺ voltage-gates are closed

• Na⁺ time-dependent gate (ball and chain) is open

Stage Two of the Action Potential

Hypopolarization (Threshold)

• Membrane is brought to threshold voltage by depolarizing stimulus

• Na⁺ voltage-dependent gates open

Stage Three of the Action Potential

Depolarization (Rising Phase)

• Na⁺ flows through open time-dependent and voltage-dependent gates

• Flow of Na⁺ into the cell rapidly depolarizes the membrane

  • Positive Feedback Loop: Na⁺ entry causes depolarization, which opens more voltage gated Na⁺ channels, which causes more depolarization

Stage Four of the Action Potential

Overshoot

• Closure of time-dependent Na⁺ gate and delayed opening of voltage-gated K⁺ channels halts membrane depolarization

Stage Five of the Action Potential

Repolarization (Falling Phase)

• Open voltage-gated K⁺ channes repolarize the membrane back to a negative membrane potential

Stage Six of the Action Potential

Hyperpolarization (Undershoot)

• Slowly closing voltage-gated K⁺ channels hyperpolarize membrane towards E_K

  • Negative Feedback Loop: voltage-gated K⁺ channels bring the action potential to an end and induce their own closing

• Na⁺ channels return to closed resting state

  • Voltage-gate is closed

  • Time-dependent gate is open

Stage Seven of the Action Potential

Return to Resting State

• Closure of voltage-gated K⁺ channels returns the membrane potential to its resting value

Rate Coding

Information is carried by how often a single neuron fires.

• A stronger stimulus increases action potential firing rate

  • Allows the threshold to be reached earlier in the refractory period

Population Coding

Information is distributed across and decoded from the joint activity of many neurons working together.

• Individual receptors differ in their sensory thresholds

• Stronger stimulus excites more receptors

Distributed Coding

A neural representation strategy where information is encoded not by a single neuron, but by the collective activity pattern of large ensemble of neurons.

• Lecture Example:

  • Three neurons:

    • Danger neuron

    • Size-sensitive neuron (Small)

    • Size-sensitive neuron (Large)

  • The brain is able to encode all four invertebrates (Fly, Bee, Mosquito, Gnat) with just these three neurons