# data[].attributes.headline
Robert Hooke's Discovery of the Cell - 1665

# data[].attributes.subject
Robert Hooke's Discovery of the Cell - 1665

# data[].attributes.body
Above is a video explaining how Robert Hooke discovered the cell including what the microscope he used looked like. He would make very detailed drawings of insects, and the microscope he used wasn’t powerful enough. He had to use his imagination to complete the drawings, but as seen in the video, they were very accurate.

Hooke coined the term “cell.” He sectioned off a piece of cork and saw round structures under the microscope, and named them cells.¹

The structures that he was looking at were the dead cell walls of plant cells, but he didn’t see the nucleus or other organelles found in living cells.²

Regardless, without Hooke’s initial discovery of the cell, further research wouldn’t have begun and ion channels would not have been discovered so it was very important.

Sources:
(1)
https://www.youtube.com/watch?v=2gtrkxtsQ2k
(2)
https://bitesizebio.com/166/history-of-cell-biology/

# data[].attributes.headline
Julius Bernstein and the Action Potential - 1868

# data[].attributes.subject
Julius Bernstein and the Action Potential - 1868

# data[].attributes.body
The photo above shows Bernstein along with the drawing of the first action potential in a nerve.¹

At this point, we know what a neuron is and what it looks like. Now, scientists could move on to the mechanisms behind it all.

In 1868, Julius Bernstein was the first to give an accurate description of the action potential. He did this using an instrument that he also developed, called the differential rheotome. This allowed him to measure the exact time and progression of electrical activity in nerves and muscles, which gave its conduction and velocity of the electrical impulse.²

He used his differential rheotome to determine that at rest, the nerve interior is about 60mV more negative with respect to the nerve exterior.³

This discovery led to more work in this field to go into more depth with the action potential, and all of the mechanisms behind it.

Sources:
(1)
https://www.researchgate.net/figure/A-Photograph-of-Julius-Bernstein-at-the-time-of-his-rectorship-at-the-University-of_fig1_330118270
(2)
https://pubmed.ncbi.nlm.nih.gov/16341542/
(3)
https://www.ionchannellibrary.com/fundamentals/history-of-ion-channels/

# data[].attributes.headline
Santiago Ramón y Cajal's Staining Technique - 1894

# data[].attributes.subject
Santiago Ramón y Cajal's Staining Technique - 1894

# data[].attributes.body
The photo above¹ shows a picture from 1894 of what the proposed neural network looked like according to the neuron doctrine. You can see the gaps at the end of each of the branches, which represent synapses.

The neuron doctrine was one of two theories proposed to say that the nervous system is composed of discrete, individual cellular units.2

Camillo Golgi developed a staining technique known as “the black reaction” that allowed the complete visibility of nerve cells. This allowed the view of a complete neuron cell as well as its cellular structures. Cajal used this information to show that there were gaps or synapses in between the neurons.²

Sources:
(1)
https://www.the-scientist.com/foundations/the-neuron-doctrine-circa-1894-38476
(2)
https://embryo.asu.edu/pages/neuron-doctrine-1860-1895

# data[].attributes.headline
Willhelm Waldeyer and the Neuron Doctrine - 1891

# data[].attributes.subject
Willhelm Waldeyer and the Neuron Doctrine - 1891

# data[].attributes.body
The photo above shows a drawing made by Cajal that explain the difference between the neuron theory and the reticular theory. This was what Waldeyer directly built off of to officially publish his discoveries.²

In 1891, Waldeyer was the first to coin the term “neuron” and the concept of the neuron doctrine. He built on all of the discoveries of past scientists, such as Golgi and Cajal, to support his findings. He proposed that the neuron was the most basic unit in the nervous system. This was fully accepted when, due to Golgi’s staining technique, people could actually see neurons in detail, and were able to confirm the existence of neural synapses.¹

Sources:
(1)
https://embryo.asu.edu/pages/neuron-doctrine-1860-1895

(2)
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/neuron-doctrine

# data[].attributes.headline
Ernest Overton and the Lipid Plasma Membrane - 1899

# data[].attributes.subject
Ernest Overton and the Lipid Plasma Membrane - 1899

# data[].attributes.body
The photo above depicts what  Overton's concept of the cell membrane looked like.2

In 1899, Charles Ernest Overton (who is actually a distant cousin of Charles Darwin!) was the first to introduce the concept of a lipid plasma membrane. The major weakness behind this theory was that the membrane had an unexplainable high permeability to water. He was one of two individuals who noticed that chemicals that are anesthetics are also the same as those that are both water-soluble and oil-soluble. This meant that a molecule has to be oil-soluble to pass through a cell membrane.¹ This was an important observation that was made, that will be built upon by other researchers.

Sources:
(1)
https://en.wikipedia.org/wiki/History_of_cell_membrane_theory#:~:text=Ernest%20Overton%20(a%20distant%20cousin,oil)%20plasma%20membrane%20in%201899.&text=Harvey%20and%20James%20Danielli%20
(2)
https://www.sciencedirect.com/science/article/pii/S0070216108610394

# data[].attributes.body
The image above¹ shows the Danielli-Davson model shows the theory of the cell membrane that was proposed by Hugh Davson and James Danielli

This model was very important because these scientists proposed a lipid bilayer that is coated on both sides with a layer of globular proteins. This protein layer didn't have a particular structure in this model.²

This theory had previously been proposed by the scientists Gorter and Grendel, but the important difference in the Danielli-Davson model is that the layers explain the observations of surface tension on the lipid bilayers that were made by Danielli. Now, we know that these are the phospholipid head groups.³

Beginning to understand the structure of the cell membrane was a crucial part in the eventual discovery of the structure of the ion channel.

Sources:
(1)
https://www.timetoast.com/timelines/history-of-the-theoretical-models-of-the-cell-membrane
(2)
https://en.wikipedia.org/wiki/History_of_cell_membrane_theory#:~:text=Ernest%20Overton%20(a%20distant%20cousin,oil)%20plasma%20membrane%20in%201899.&text=Harvey%20and%20James%20Danielli%20(1939,for%20measurements%20of%20surface%20tension.
(3)
https://en.wikipedia.org/wiki/Davson%E2%80%93Danielli_model

# data[].attributes.headline
Cole and Baker's Research of Voltage-Gated Membrane Pores - 1941

# data[].attributes.subject
Cole and Baker's Research of Voltage-Gated Membrane Pores - 1941

# data[].attributes.body
The paper above is one written by Kenneth Cole and Richard Baker about their research on the properties of squid axons during measurement of their AC electrical properties.¹

These researchers made a direct and important impact on the discovery of voltage-gated membrane pores. Their research on the giant squid axon led directly to the discovery of the voltage-gated membrane pores and how these pores are an important and critical part of neurotransmission.²

Sources:
(1)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238007/
(2)
http://dbkgroup.org/Papers/pethig_kell_pmb87.pdf

# data[].attributes.attachment_link.readable_text
Longitudinal alternating current impedance measurements have been made on the squid giant axon over the frequency range from 30 cycles per second to 200 kc. per second. Large sea water electrodes were used and the inter-electrode length was immersed in oil. The impedance at high frequency was approximately as predicted theoretically on the basis of the poorly conducting dielectric characteristics of the membrane previously determined. For the large majority of the axons, the impedance reached a maximum at a low frequency and the reactance then vanished at a frequency between 150 and 300 cycles per second. Below this frequency, the reactance was inductive, reaching a maximum and then approaching zero as the frequency was decreased. The inductive reactance is a property of the axon and requires that it contain an inductive structure. The variation of the impedance with interpolar distance indicates that the inductance is in the membrane. The impedance characteristics of the membrane as calculated from the measured longitudinal impedance of the axon may be expressed by an equivalent membrane circuit containing inductance, capacity, and resistance. For a square centimeter of membrane the capacity of 1 µf with dielectric loss is shunted by the series combination of a resistance of 400 ohms and an inductance of one-fifth henry.

# data[].attributes.attachment_link.title
LONGITUDINAL IMPEDANCE OF THE SQUID GIANT AXON

# data[].attributes.attachment_link.description
Longitudinal alternating current impedance measurements have been made on the squid giant axon over the frequency range from 30 cycles per second to 200 kc. per second. Large sea water electrodes were used and the inter-electrode length was immersed ...

# data[].attributes.headline
Alan Hodgkin and Andrew Huxley's Work on the Action Potential - 1952

# data[].attributes.subject
Alan Hodgkin and Andrew Huxley's Work on the Action Potential - 1952

# data[].attributes.body
The image above¹ shows the Hodgkin-Huxley model. The components of this circuit represent the components in a neural propagation sequence. The lipid bilayer is the capacitance (Cm). Voltage gated and ion leak channels are the nonlinear(gn) and linear (gL). Electrochemical gradients are the batteries (E). Ion pumps and exchangers are the current sources (Ip).¹

The Hodgkin-Huxley model, also known as the conductance-based model, was used to represent how action potentials work in a neuron. The model consists of a series of equations that approximate the electrical characteristics of excitable cells like neurons and cardiac myocytes. These scientists received a Nobel Prize for their discovery.1

Sources:
(1)
https://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model

# data[].attributes.headline
Bernard Katz and Ricardo Miledi's Work With Ion Channels - 1960s

# data[].attributes.subject
Bernard Katz and Ricardo Miledi's Work With Ion Channels - 1960s

# data[].attributes.body
The photo above² shows what an ion channel looks like. The discoveries made by Katz and Miledi would directly contribute to the knowledge of the structure of the ion channel.

Katz and Miledi published a paper on using noise analysis to officially confirm the existence of ion channels. After a steady application of acetylcholine, minute stochastic fluctuations were observed in the membrane potential. Katz and Miledi were able to deduce basic properties of the ion channel by studying the spectral density of this noise.¹

Sources:
(1)
https://www.nature.com/articles/nn0703-659
(2)
https://en.wikipedia.org/wiki/Ion_channel

# data[].attributes.headline
Erwin Neher and Bert Sakmann's Research with Patch Clamps - late 1970s, early 1980s

# data[].attributes.subject
Erwin Neher and Bert Sakmann's Research with Patch Clamps - late 1970s, early 1980s

# data[].attributes.body
The image above¹ shows a recording using the patch clamp technique. It shows the transitions between two conductance states of a single ion channel.

Neher and Sakmann developed and used this patch clamp technique to, for the first time, record the currents in a single ion channel molecule. This helped improve the understanding of the involvement of channels in processes like action potentials and nerve activity.¹

Sources:
(1)
https://en.wikipedia.org/wiki/Patch_clamp

# data[].attributes.headline
Roderick MacKinnon - The Nobel Prize Winner! - 2003

# data[].attributes.subject
Roderick MacKinnon - The Nobel Prize Winner! - 2003

# data[].attributes.body
The photo above¹ depicts Robert MacKinnon, who won a Nobel Prize for his work on the structure of the ion channel. MacKinnon was born in Massachussets, and received his MD in 1982, receiving training in Internal Medicine at the Beth Israel Hospital in Boston.²

MacKinnon's work shed a whole new light on how ion channels actually allow ions to pass through. He also shared the discovery of how an ion can be closed or open to allow some ions through, and not others (called selectivity). MacKinnon's discovery built upon many that came before him, including Neher and Sakmann, Hodgkin and Huxley, and many more.

Sources:
(1)
https://jasn.asnjournals.org/content/15/4/1096
(2)
https://en.wikipedia.org/wiki/Roderick_MacKinnon#:~:text=MacKinnon%20was%20born%20in%20Burlington,the%20University%20of%20Massachusetts%20Boston.&text=After%20receiving%20his%20degree%20from,Beth%20Israel%20Hospital%20in%20Boston.

# data[].attributes.headline
Contemporary: Coronavirus Proteins as Ion Channels

# data[].attributes.subject
Contemporary: Coronavirus Proteins as Ion Channels

# data[].attributes.body
This article, from October 2020, discusses ion channels and their importance with the current SARS-CoV-2 virus pandemic that we are in right now. The article highlights that the ion channel activity within the CoV proteins could potentially be used in a therapeutic aspect.¹

Specifically, the E (envelope) protein which is embedded into the virus' bilayer has specific inflammatory properties that are related to its being an ion channel protein, and has specific ion conductances in the membrane. The photo above¹ shows the structure of the E channel protein.

This is very relevant today in that this specific protein may hold an answer to the global pandemic that we are in the midst of. The virus affects all parts of our bodies, including our nervous systems so I believe that this research is important to be highlighted and discussed.

Sources:
(1)
https://www.frontiersin.org/articles/10.3389/fimmu.2020.573339/full