Ionic Basis of Resting and Action Potentials

Hello! Welcome to the first lesson of our second module.

In the previous module, we built a solid foundation in the electronic principles of biomedical measurement. We covered how to amplify faint biological signals, filter them to isolate the frequencies of interest, and protect them from a variety of noise sources. We finished by learning to quantify signal quality using the Signal-to-Noise Ratio (SNR).

Now, we pivot from the "how" of measurement to the "what." This lesson begins Module 2, "Sensing Bioelectric Potentials," by addressing the fundamental question: where do these electrical signals come from in the first place? Our learning outcome is to explain the ionic basis of resting and action potentials in excitable cells (like neurons and muscle cells).

This is the bedrock of electrophysiology. For your work at Neuraease, understanding how individual neurons "fire" is the first step toward making sense of the complex signals like EEG that arise from the coordinated activity of millions of these cells.

The Cell at Rest: An Uneasy Equilibrium

An "excitable" cell, like a neuron, is essentially a tiny biological battery. At rest, it maintains a stable voltage across its membrane, known as the resting membrane potential. This potential is the source of stored energy that the cell will use to generate an electrical signal.

To understand how this battery is created and maintained, let's watch a short video that lays out the key components.

Let's break down the key mechanisms that establish the resting potential (typically around -70 mV):

1. Unequal Ion Concentrations: The sodium-potassium pump is a protein that actively uses energy (in the form of ATP) to shuttle ions across the membrane against their concentration gradients. It tirelessly pumps 3 Na+ ions out for every 2 K+ ions it pumps in. This creates a high concentration of K+ inside the cell and a high concentration of Na+ outside the cell.
2. Selective Permeability: The cell membrane has leak channels that are always open. Crucially, at rest, the membrane has many more K+ leak channels than Na+ leak channels. This makes the resting membrane far more permeable to K+ than to Na+.
3. Electrochemical Equilibrium:
   • Because the membrane is permeable to K+, these positively charged ions begin to leak out of the cell, moving down their concentration gradient (from high to low concentration).
   • As K+ ions leave, they take their positive charge with them, leaving behind a net negative charge inside the cell (from proteins and other anions that are too large to leave).
   • This growing negative charge inside the cell creates an electrical force that starts to pull the positive K+ ions back in.
   • An equilibrium is reached when the outward chemical force (diffusion) on K+ is perfectly balanced by the inward electrical force. The membrane potential at which this balance occurs is called the equilibrium potential for K+ (E_K), which is around -90 mV.

Since the resting membrane is overwhelmingly permeable to K+, the overall resting membrane potential of about -70 mV is very close to potassium's equilibrium potential.

The Nernst and Goldman Equations

Given your engineering background, you'll appreciate that these relationships can be described mathematically.

The Nernst equation calculates the equilibrium potential for a single ion species. It quantifies the exact voltage needed to balance the diffusion force for a given concentration gradient.

$E_{ion}=\frac{RT}{zF}\ln \frac{[ion{]}_{out}}{[ion{]}_{in}}$

Where:

• $R$ is the ideal gas constant
• $T$ is the absolute temperature
• $z$ is the valence (charge) of the ion
• $F$ is Faraday's constant
• $[ion{]}_{out}$ and $[ion{]}_{in}$ are the ion concentrations outside and inside the cell.

A more comprehensive model is the Goldman-Hodgkin-Katz (GHK) equation, which calculates the overall membrane potential by considering the contributions of all major ions (Na+, K+, and Cl-) weighted by their relative permeabilities ($P$).

$V_m=\frac{RT}{F}\ln \left(\frac{P_K[K^{+}{]}_{out}+P_{Na}[N{a}^{+}{]}_{out}+P_{Cl}[C{l}^{-}{]}_{in}}{P_K[K^{+}{]}_{in}+P_{Na}[N{a}^{+}{]}_{in}+P_{Cl}[C{l}^{-}{]}_{out}}\right)$

The key insight from the GHK equation is that the ion with the highest permeability has the greatest influence on the membrane potential. At rest, $P_K\gg P_{Na}$, which is why $V_m$ is close to $E_K$.

To see a practical application of the Nernst equation and how it proves the importance of potassium, watch the following segment.

The Action Potential: Firing a Signal

The resting potential is the baseline. The action potential is the signal itself—a rapid, temporary, and dramatic reversal of the membrane potential. It is an "all-or-none" event: once a certain threshold is reached, it fires with a consistent amplitude and shape.

Let's return to our first video to see how this happens.

The image below provides a fantastic summary of the entire process, linking the voltage changes to the state of the ion channels.

Let's walk through the phases using this diagram:

1. Resting State: Both voltage-gated Na+ and K+ channels are closed. The membrane potential is stable at ~-70 mV.
2. Threshold: A stimulus causes an initial depolarization. If the membrane potential reaches the threshold (around -55 mV), the action potential is triggered.
3. Depolarization (Rising Phase): Voltage-gated Na+ channels open quickly. Driven by strong electrical and chemical gradients, Na+ ions rush into the cell. This massive influx of positive charge causes the membrane potential to skyrocket to about +30 mV.
4. Repolarization (Falling Phase): The Na+ channels inactivate (a second gate closes, blocking the channel). Simultaneously, the slower voltage-gated K+ channels fully open. Now K+ ions rush out of the cell, taking their positive charge with them and causing the membrane potential to fall rapidly.
5. Hyperpolarization (Undershoot): The K+ channels are slow to close. They remain open long enough for the potential to briefly dip below the resting potential.

During and immediately after the action potential, the neuron enters a refractory period:

• Absolute Refractory Period: While the Na+ channels are inactivated, it is impossible to fire another action potential. This ensures the signal propagates in one direction down the axon.
• Relative Refractory Period: During hyperpolarization, a stronger-than-usual stimulus is required to reach threshold. This mechanism allows the frequency of action potentials to encode the intensity of a stimulus.

Test your understanding!

Imagine you are developing a drug that selectively blocks voltage-gated K+ channels. How would this drug affect the shape of the action potential?

1. Would it affect the resting membrane potential?
2. Would it affect the depolarization (rising) phase?
3. How would it change the repolarization (falling) phase and the overall duration of the action potential?

Show answer

1. Resting Potential: It would have little to no effect. The resting potential is primarily maintained by K+ leak channels and the Na+/K+ pump, not the voltage-gated K+ channels, which are closed at rest.
2. Depolarization: It would not affect the rising phase. Depolarization is caused by the opening of voltage-gated Na+ channels.
3. Repolarization: This is where the major effect would be. Repolarization depends on the efflux of K+ through voltage-gated K+ channels. Blocking these channels would prevent or dramatically slow down the repolarization process. The membrane would take much longer to return to its resting potential, significantly prolonging the duration of the action potential.

For a detailed textual explanation to complement the videos, the following article is a useful resource.

Conclusion

In this lesson, we've gone to the very source of bioelectric signals. We've seen how cells are not passive wires but are active, complex electrochemical machines that generate signals through the precise, coordinated movement of ions across a semipermeable membrane.

Key Takeaways:

• The resting membrane potential (~-70 mV) is established by high intracellular K+ and high extracellular Na+ (maintained by the Na+/K+ pump), and the membrane's high permeability to K+ at rest.
• The action potential is an all-or-none electrical spike triggered when a stimulus depolarizes the membrane to a threshold potential.
• The rising phase (depolarization) is caused by a rapid influx of Na+ through voltage-gated Na+ channels.
• The falling phase (repolarization) is caused by the inactivation of Na+ channels and the efflux of K+ through voltage-gated K+ channels.
• Refractory periods limit the firing rate and ensure the unidirectional propagation of the signal.

Preview of the Next Lesson:
We now understand how a single neuron generates a signal. But neurons don't exist in isolation. In the next lesson, we will zoom out to see how these cells are organized, covering the learning outcome: Describe the basic structure and function of the peripheral and central nervous systems. This will provide the anatomical context for understanding how signals travel through the body and are processed in the brain.