Reduction and Integration of the Neurobiological Concept of “Action Potential”

This Spring, I took a Saturday course at the local community college on Anatomy and Physiology. (It’s the course that people going into the medical professions, such as nursing, would take.) The textbook used was “Fundamentals of Anatomy and Physiology”, 11th Ed. (Martini, Nath, Bartholomew). The following was an issue that I ran into several times while reading the textbook, and how I solved that problem to advance my understanding of the concepts. (If anyone is interested, I made an A in the course.)

Chapter 12 of the textbook presents the concept of the “action potential” in nervous tissue.

The problem is it presents everything on a microscopic level, with a very abstract presentation of the electro-chemical processes.

Before I begin, I should go over the “textbook” explanation of what an “action potential” is, as best I understand it. (Keep in mind I’m not a scientist, much less a biologist, so this is just my best understanding.)

Neurons communicate with each other via electrical signals known as “action potentials”. These are defined as brief changes in the voltage across the membrane of a neuron due to the flow of certain ions into and out of the neuron. https://teachmephysiology.com/nervous-system/synapses/action-potential/

At pages 410-411 of the textbook, a series of diagrams are presented to show the generation of an action potential in a neuron. These include 4 steps in the action potential generation process: (1) Depolarization to threshold, (2) Activation of sodium ion channels and rapid depolarization, (3) Inactivation of sodium ion channels and activation of potassium ion channels to start repolarization of the neuron, and (4) time lag in closing all potassium ion channels, which leads to temporary hyperpolarization:

 

 

IMG_6197 IMG_6198

The diagrams in the textbook show what happens at a molecular or cellular level, with each diagram containing a little picture of what is supposed to be  a voltmeter to show what the voltage of the neuron’s inner membrane is at each point in the generation of the action potential. At resting membrane potential, the neuron’s inner voltage is -70mV. There are sodium ion channels that are closed at resting membrane potential. When depolarization occurs, the stimulus causes the voltage of the inner part of the neuron to become less negative, which causes the sodium ion channels to open, which allows sodium, a positive ion, to rush into the neuron. Since sodium is a positive ion, it causes the inner portion of the neuron to become much less negative, until it is a little bit positive. (+10mV according to the textbook). As the inner portion of the neuron continues to get more positive, it causes the sodium ion channels to close, and potassium ion channels to open. Repolarization can now occur, as potassium ions, which are positive are removed from the inside of the neuron, causing it to become more negative in charge on the inside. Eventually, the neuron’s inner portion is back around -70 mV.

The above explanation is what you can get from the book, but I was dissatisfied with this explanation. I wanted to know how scientists could have reached this conclusion.  Clearly, they didn’t just have a divine revelation from God. Since this all occurs on a microscopic, molecular level, you cannot see this process happening with your naked eye. In particular, I was bothered by the way the textbook presented the voltage differentials created by the change in sodium and potassium levels in the neuron. How could they get a voltmeter small enough to insert into a neuron to measure the voltage differentials? How could they possibly know that?

In the past, this would have probably taken a trip to the library, and looking through several books on the history of biology. (This is still probably the best way.) But, with the Internet, I started with some key-word searches on a search engine. I did this research several months ago, so I am somewhat recreating what I did, but as best I can recall, this is what I started my Internet search with: “discovery of action potential”.  From that, I found the following web site: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500626/

This article discussed a pair of scientists, Alan Hodgkin and Andrew Huxley, who did research in this area about 60 years ago.  I then plugged “Alan Hodgkin and Andrew Huxley” into another search engine, and got the following Wikipedia page:

https://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model

(A side-note on Wikipedia. I don’t consider it to be a reliable source, but I do consider it useful as a “jumping off point” for research. I will read the Wikipedia article, then look at the citations, and see if I can find more reliable sources on a topic from there. I think this is a perfectly acceptable use of Wikipedia.)

From reading the above Wikipedia article, I saw that they studied something called a “squid giant axon”. There was another Wikipedia article on that topic:

https://en.wikipedia.org/wiki/Squid_giant_axon

This article said:

The large diameter of the axon provided a great experimental advantage for Hodgkin and Huxley as it allowed them to insert voltage clamp electrodes inside the lumen of the axon.”

To confirm this with a more reliable source, I then typed into a search engine: “why did they use the squid giant axon to study the action potential” From there, I found this article:

A, John Zachary Young (1907–1997). His discovery of the squid giant axon in the 1930s was pivotal since it provided an electrically excitable membrane of sufficient area for Hodgkin and Huxley’s experiments.”

Both Hodgkin and Huxley have stated that, following the failed attempts with the mercury droplets, it was the other who made the suggestion that a fine capillary electrode might be inserted inside the nerve fibre (Fig. 3A) to record the potential difference across the membrane.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424716/

Basically, this particular squid neuron is very big. About 1 mm in diameter, and several centimeters long. https://www.researchgate.net/figure/The-squid-giant-axon-The-giant-axon-is-a-very-large-up-to-1-mm-in-diameter-and-long_fig2_276491039

After that, I understood how they could have measured the change in voltage in the inner membrane of a neuron. Scientists found a neuron that was big enough to let them insert the probe of a voltmeter into it. They then operated under the assumption that this particular squid neuron worked the same as other, smaller neurons, in other species, which seemed like a reasonable inference to me. (Given the fact that all animals are connected to each other by a common ancestor in our evolutionary past, it makes sense that once a particular biological system occurs, the same model will be “used” by evolution in other organisms.)

By looking at some of the history, I learned something about the scientific experiments and observations that went into formulating this abstract idea of the action potential. I was sufficiently satisfied from half an hour of Internet searches as to how they had arrived at this conclusion, that I could move on to the rest of my reading.

I hasten to add that sometimes I might not be able to find anything regarding how scientists arrived at an abstract idea presented in a science textbook. I am somewhat limited by time constraints, and this method does not always bear fruit in 15 minutes to half an hour of Internet searches. In those instances, I will sometimes just have to resign myself to memorizing the abstract model well enough to spit it back out on a test. When that occurs, I just recognize in my mind that I haven’t really learned anything. (If I have time later, I will go back and try to learn something about how scientists came up with this idea, but sometimes I don’t.) It’s somewhat disheartening that our educational system encourages rote memorization over actual learning of concepts, but as a student, you just have to recognize that the system is what it is, and do your best to operate in it. However, I try to keep my level of rote memorization like this to a minimum, since I think if you make this your habitual method of studying in high school and college, you’ll leave academia worse than an ignoramus. So, I recommend trying to use the method outlined here at least 80 to 90 percent of the time. At the very least, you’ll have questions in your mind, that, later on down the road, might lead you to the answers.

I should also say something about where I acquired this methodology of studying science textbooks. Since this method is also an idea, I didn’t just get it through divine revelation. (We get nothing through divine revelation.)

By studying the ideas of Ayn Rand, I learned that all knowledge starts with observation, that is our sensory-perceptual apparatus. From reading “Objectivism: The Philosophy of Ayn Rand”, by Leonard Peikoff in college, I learned about the methods of “reduction” and “integration”, which relate to a concept’s “hierarchy” and “context”. Basically, integration, concerns the logical relationship of a concept to other concepts -that is, placing it in a context. For instance, above, I said that scientists assumed that the giant squid neuron was basically the same in its operation as the neurons in the human body, despite the size difference. I said this assumes that all animals share a common ancestor, which is a well-founded idea, based in Darwin’s theory of evolution through natural selection.  So, evolution through natural selection would form part of the context through which this idea of the action potential in neurons would be based.

“Reduction” relates to mentally following  a “chain” or “hierarchy” of ideas back to what you can perceive in the world around you. For instance, scientists can use a voltmeter, which has known properties to measure something that is imperceptible, the voltage of a neuron. They know through other experiments that certain voltages can perform certain tasks, such as lighting a light bulb, or spinning a turbine, etc. Chemists also are able to relate the concentrations of certain substances, like sodium, to the generation of voltage, which tells them something about the nature of otherwise imperceptible sodium atoms (that they are ions, which are charged atoms, with too few or too many electrons.) The important point of reduction here is that you want to develop a method or experiment to allow you to relate the unperceived to that which is perceived by your senses.

This explanation of Ayn Rand’s ideas on logic and epistemology is just a brief sketch. If you want to understand it better, I recommend that you pick up some of her books on the subject, or Leonard Peikoff’s book, read them, and decide for yourself if they relate to reality or not.  Like all ideas, you shouldn’t take them on faith, or assume that they are revelations from God.