Resting Membrane Potential and Action Potential

A note on sources

PART 1 - RESTING MEMBRANE POTENTIAL (RMP)

1.1 What Is the RMP?

"The resting membrane potential of large nerve fibers when they are not transmitting nerve signals is about −70 mV. That is, the potential inside the fiber is 70 mV more negative than the potential in the extracellular fluid on the outside of the fiber."

• Guyton and Hall, p. 78

1.2 The Na⁺-K⁺ Pump (Electrogenic Pump)

• Pumps 3 Na⁺ OUT for every 2 K⁺ IN
• Creates a net loss of positive charges from inside the cell
• Is therefore electrogenic - it directly contributes about -4 mV to the RMP

1.3 K⁺ Leak Channels and the Potassium Diffusion Potential

If only K⁺ could cross the membrane, the Nernst potential for K⁺ (K_in/K_out = 35) = -94 mV

If only Na⁺ could cross, the Nernst potential for Na⁺ (Na_in/Na_out = 0.1) = +61 mV

1.4 The Goldman Equation - Combining All Ions

• Diffusion of K⁺ and Na⁺ together → -86 mV
• Adding the electrogenic pump contribution (−4 mV) → net ≈ −90 mV

1.5 Stuart Fox's Emphasis on RMP

1. Equilibrium potential - for each ion, there is a voltage at which the electrical force exactly balances the diffusion force (Nernst potential). K⁺ equilibrium potential ≈ -90 mV; Na⁺ equilibrium potential ≈ +60 mV.
2. Relative permeability - the resting RMP of -70 mV is a compromise between these two opposing equilibrium potentials, weighted heavily toward K⁺ because of its much higher resting permeability.

"Relative membrane permeability to K⁺ is the essential factor that produces resting membrane potential." - Fox Ch. 7

PART 2 - ACTION POTENTIAL (AP)

2.1 Overview

2.2 Phases of the Action Potential

Phase 1 - Resting Stage

• Membrane potential = -70 mV
• Membrane is said to be "polarized"
• Voltage-gated Na⁺ channels: CLOSED (activation gate shut, inactivation gate open)
• Voltage-gated K⁺ channels: CLOSED

Phase 2 - Depolarization

• A stimulus depolarizes the membrane to the threshold (~-55 mV, or about 15 mV above resting)
• At threshold, voltage-gated Na⁺ channels snap open rapidly
• Na⁺ rushes IN along its electrochemical gradient (Na⁺ is high outside, and the inside is negative)
• Membrane potential shoots up: -70 mV → 0 mV → +35 mV (overshoot)
• This is a positive feedback cycle - Na⁺ entry makes inside more positive → more Na⁺ channels open → more Na⁺ enters

"This process is a positive-feedback cycle that, once the feedback is strong enough, continues until all the voltage-gated sodium channels have become activated (opened)."

• Guyton and Hall, p. 82

Phase 3 - Repolarization

• Within a fraction of a millisecond of opening:
  • Na⁺ channels inactivate (the inactivation gate closes) - Na⁺ entry stops
  • Voltage-gated K⁺ channels open (delayed, slower response)
• K⁺ rushes OUT, restoring the negative charge inside
• Membrane returns from +35 mV back toward -70 mV

Phase 4 - Hyperpolarization (Undershoot / After-Hyperpolarization)

• K⁺ channels stay open slightly longer than needed → membrane overshoots past -70 mV → becomes briefly more negative (e.g., -75 to -80 mV)
• As K⁺ channels close, membrane returns to normal resting -70 mV

2.3 Voltage-Gated Channels: The Molecular Machinery

Voltage-Gated Na⁺ Channel - Three States:

"The same increase in voltage that opens the activation gate also closes the inactivation gate. The inactivation gate, however, closes a few 10,000ths of a second after the activation gate opens."

• Guyton and Hall, p. 81

Voltage-Gated K⁺ Channel:

• Has one gate; opens slowly during depolarization (takes ~10x longer than Na⁺ channel)
• Opens at the peak of the AP, driving repolarization
• Closes slowly → causes the hyperpolarization undershoot

Stuart Fox adds - Sodium Conductance vs. Potassium Conductance:

2.4 Threshold and the All-or-Nothing Principle

• Threshold is reached when the inward Na⁺ current exceeds the outward K⁺ current
• A depolarization of 15-30 mV from rest is typically needed (from -70 mV up to about -55 mV)
• Once threshold is crossed, a full AP fires regardless of stimulus strength - this is the all-or-nothing principle
• Subthreshold stimuli cause only local, graded potentials that fade without propagating

2.5 Propagation of the Action Potential

1. The depolarized region creates local circuits of ionic current flow - positive ions flow inward through the depolarized zone, then spread along the axon core
2. These currents depolarize adjacent membrane segments to threshold
3. New APs fire in adjacent regions
4. The wave of depolarization travels down the entire length of the fiber

"The arrows show a local circuit of current flow from the depolarized areas of the membrane to the adjacent resting membrane areas...the sodium channels in these new areas immediately open...and the explosive action potential spreads."

• Guyton and Hall, p. 84

2.6 Myelination and Saltatory Conduction

• Much faster (up to 120 m/s in large myelinated fibers vs. 0.5 m/s in unmyelinated)
• Energetically efficient (Na⁺/K⁺ pumps only need to restore ions at the nodes)

2.7 Refractory Periods

"The period during which a second action potential cannot be elicited, even with a strong stimulus, is called the absolute refractory period...about 1 millisecond. Therefore, one can readily calculate that such a fiber can transmit a maximum of about 1000 impulses per second."

• Guyton and Hall, p. 84

• Ensure APs travel in one direction only (the region behind the AP is in absolute refractory period)
• Set a maximum firing frequency (~1000/sec for large myelinated fibers)

2.8 Calcium's Role (Guyton)

• Normal extracellular Ca²⁺ stabilizes the sodium channel by binding to the exterior and raising the threshold for Na⁺ channel activation
• Hypocalcemia (low Ca²⁺) → reduced threshold → spontaneous nerve firing → tetany
• Hypercalcemia → elevated threshold → reduced excitability
• Voltage-gated Ca²⁺ channels (slow channels) also contribute to APs in cardiac and smooth muscle

2.9 Energy Metabolism After Action Potentials

COMPARISON: Guyton & Hall vs. Stuart Fox

Summary Flow (Both Books)

RMP (-70 mV)
    │
    │ ← Stimulus (depolarization to threshold ~-55 mV)
    ▼
Positive feedback: Na⁺ channels open → Na⁺ rushes in → more channels open
    │
    ▼
Depolarization → Overshoot (+35 mV)
    │
    ▼
Na⁺ channels inactivate → K⁺ channels open → K⁺ rushes out
    │
    ▼
Repolarization → Hyperpolarization (undershoot)
    │
    ▼
K⁺ channels close → Return to RMP (-70 mV)
    │
    ▼
Na⁺-K⁺ pump restores concentration gradients (slow, metabolic)

• All quoted content and diagrams: Guyton and Hall Textbook of Medical Physiology, 14th ed., Chapter 5 (pp. 77-89)
• Stuart Fox Ch. 7 content: PCB 4701 Action Potential lecture materials, based on Fox's Human Physiology, 14th ed.