Action Potentials: Aqueous Environment Inside the Cell and Ion Distribution

Background of the Human Body's Ability to Generate Electricity


Now that we are already looking at the various ion channels present in the cell membrane, let’s take a moment to highlight the important roles they play in the process of generating electrical signals.


In the human body, muscles are typically classified into three types: skeletal muscles, which are attached to bones; cardiac muscles, which contract the heart; and smooth muscles, which control the movements of internal organs. Depending on whether we can willfully control them, they can be divided into voluntary and involuntary muscles, or classified based on their appearance as striated or non-striated. However, all these muscles share a common characteristic: they operate based on electrical signals known as action potentials. We also know that neurons, or nerve cells, transmit electrical signals. The heartbeat, digestive processes in the stomach, nutrient absorption in the intestines, and our ability to walk and run—all of these actions are driven by electrical signals. So, is the human body like a small battery that generates electricity? Are we the only ones? Aren't there electric eels that generate more electricity than us? Let’s first examine the fundamental background that allows the human body to generate electricity.


1. The inside and outside of the cell consist of liquid environments 

The largest component that makes up the human body is water. In this watery environment, all biochemical processes essential for life and the maintenance of life occur. It is said that in infants, water constitutes about 75% of body weight, while in adults, it makes up about 50-60%. So, where is all this water located in the human body? The water within the body, or body fluids, can be divided into intracellular fluid (ICF) and extracellular fluid (ECF). Intracellular fluid fills the entire space inside the cell, known as the cytoplasm. Extracellular fluid is further divided into interstitial fluid, which fills the space between cells, and intravascular fluid (plasma, lymph, and cerebrospinal fluid). Intracellular fluid accounts for about 40% of total body weight, while extracellular fluid accounts for about 20%, with plasma making up about 5% and interstitial fluid about 12%. [1]



The composition of intracellular fluid and extracellular fluid varies depending on the tissues and organs in which they are located. However, even though the components that make up these two fluids are different, the water between the two always maintains an osmotic equilibrium. This is because, when an osmotic gradient exists, water moves in and out through channels such as aquaporins that connect the inside and outside of the cell.


2. Compartmentalization through membranes

Various ions dissolved in water, or solutes, cannot easily permeate the cell membrane due to their large size or charge, so they move in and out of the cell using different ion channels. Interestingly, the liquid environment inside the cell is not uniform. The aqueous environment within the cell differs in composition because individual organelles are mostly surrounded by membranes, distinguishing them from the cytoplasm, and they must have their own specific pH and ionic composition based on their roles within the cell. This process of trapping specific solutes at different concentrations in designated areas is known as compartmentalization [2], and it is a physiologically crucial phenomenon. For example, lysosomes, which are responsible for breaking down biological materials, must operate in a highly acidic environment to effectively dissolve their contents. If cardiac cells were unable to store calcium in the sarcoplasmic reticulum, the heart would not be able to contract, as calcium ions play a critical role in generating action potentials for heart contractions. This topic will be explored in more detail in the context of intracellular signaling processes later on.


3. Ion concentration control

By utilizing various forms of ion channels to regulate the ion concentrations inside and outside the cell, it becomes possible to control the environments both intracellularly and extracellularly, enabling several essential functions for life. One of these functions is the generation of electricity. 


What is the relationship between ion channels and electrical signals? The state in which an atom loses or gains electrons is called an "ion" state. Since electrons carry a negative charge, losing electrons results in a relative positive charge, creating a "cation," while gaining electrons leads to a relatively greater negative charge, forming an "anion." These ions, which possess the electrical property of "charge," exist in the intracellular fluid and extracellular fluid as electrolytes.


Electrolyte: The significance of the ion distribution 

One important aspect we must pay close attention to is the distribution of ions inside and outside the cell. The reason these ions, commonly referred to as electrolytes, are of great importance in physiology is not only because they are responsible for the electrical activity of cells, but also because electrolyte deficiencies are well-known to have various effects on the human body. In short, if ions are evenly distributed inside and outside the cell, the cell cannot generate electricity.


Ion distribution inside and outside the cell


Intracellular fluid primarily contains potassium ions (K+), phosphate anions (HPO4²-), magnesium ions (Mg²+), and proteins, while extracellular fluid is mainly composed of sodium ions (Na+) and chloride anions (Cl-). This distribution results in the formation of electrical polarity around the cell membrane. Due to the negatively charged phosphates and the large size of the negatively charged proteins, the interior of the cell becomes relatively more negative compared to the outside. However, because phosphates and proteins are too large to exit the cell, the ions carrying charge are the ones that can dynamically influence the electrical polarity of the intracellular and extracellular environments. Molecules such as oxygen, carbon dioxide, and glucose that move in and out of the cell do not carry electrical charge, and thus their distribution and movement do not affect the electrical polarity of the cell, making them irrelevant to the generation of electricity. The ions are the main players.


Inside the cell, potassium ions (K+) dominate, while sodium ions (Na+) and chloride ions (Cl-) are the primary ions outside the cell. When charged ions flow in a specific direction, we refer to this as electrical current, and their movement affects the total amount of positive and negative charges inside and outside the cell. Regarding this, let’s briefly touch on the concept of "gradient."


Chemical Gradient and Electrical Gradient: Two Different Forces

In previous article, we examined the movement of various substances in and out of the cell, that is, diffusion. Substances naturally move from areas of high concentration to areas of low concentration without any external forces acting upon them. Isn't this the same principle that people moving from a crowded room to a quieter one without anyone directing them? However, the direction of diffusion is not only influenced by the chemical gradient.


Let's take potassium ion (K+) as an example. K+ is found at a significantly higher concentration inside the cell, with an internal concentration that is about 30 times greater. Uniquely, the K+ ion channels are usually slightly open (leaky channel), unlike other ion channels. Considering the direction of diffusion according to the chemical gradient, it would seem natural for K+ to move through the open channels toward the lower concentration outside the cell. However, K+ does not rapidly move out of the cell while maintaining an extremely high concentration inside. This is because a strong negative charge formed inside the cell strongly attracts the positively charged K+. Opposite charges attract, while like charges repel, right? Both the chemical gradient and the electrical gradient are acting on K+, and over time, the strength of these two different forces will stabilize and reach an equilibrium state. When this state is measured with a voltmeter, the voltage inside the cell is typically recorded at around -90 mV. This indicates that the inside of the cell carries a relative negative charge compared to the outside.


Differences in the Electrochemical Gradients of Potassium and Sodium

Non-polar substances diffuse in one direction until they reach equilibrium, but polar ions are influenced not only by the chemical concentration but also by the electrical concentration, meaning that both forces together, called the electrochemical gradient, act on these ions. Let’s also consider sodium ions (Na+), which are distributed at high concentrations outside the cell. In this case, both the chemical gradient and the electrical gradient act in the same direction. The force of the chemical gradient, which seeks to move Na+ into the cell where the concentration is lower, and the strong negative charge pulling it inward create a tendency for Na+ to move into the cell. However, unlike K+ channels, Na+ channels are usually closed and only open under specific conditions, which is why a high concentration is maintained outside the cell.



Another important point to consider is the role of the Na+/K+ pump. This pump uses ATP to actively transport three Na+ ions out of the cell while simultaneously bringing two K+ ions into the cell. There is a clear reason for this: it generates electricity by utilizing the state where Na+ is more abundant outside the cell and K+ is more abundant inside.


We have examined how ions with a charge freely exist in the aqueous environments inside and outside the cell, and how those with polarity can move in and out of the cell based on concentration differences with the help of membrane proteins known as ion channels. We have also looked at the electrical polarity formed inside and outside the cell membrane. In the next article, we will explore the process by which electricity is generated at the cell membrane based on this environmental characteristics.



[References]

[1] Physiology, Body Fluids

https://www.ncbi.nlm.nih.gov/books/NBK482447/


[2] Essential cell biology, Fifth edition. New York: WW Norton & Company, [2019]  





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