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READING Editor's Note
: In September last year, the Frontiers for Young Minds journal website (hereinafter referred to as "FYM") launched a collection of scientific articles written by five Nobel Prize winners specifically for teenagers, and "Mr.
Sai" was officially authorized by FYM to release Chinese translation for the first time
.
This November, the FYM Nobel Prize Collection series was updated with five new articles
written by Nobel laureates for curious brains around the world.
"Mr.
Sai" is exclusively authorized by FYM and will translate these five articles and share them with Chinese readers
.
Currently, the collection includes the following articles: "Nobel Laureates Interpreting Gravitational Waves:
A New Window into the Universe" – 2017 Nobel Laureate in Physics Barry Barish
My RNA research path
is how cells communicate with each other
.
The presence of cell membranes allows each cell to maintain a stable internal environment to perform its own special functions
.
: communication
between nerve cells, nerve cells are the basic components of the brain, and their communication relies on "electrical language"
.
At each given moment, each nerve cell exhibits specific electrical activity, producing a set of brief electrical impulses called peak potentials
.
In the process of brain activity, the entire network of nerve cells will constantly produce peak potentials, like playing a harmonious "electric symphony"
.
Such electrical activity is closely related to
our rich actions, thoughts, feelings, and memories.
In order to play this "electric symphony", how do nerve cells communicate with each other? In fact, communication between nerve cells is much more complex than communication between other cell types because it involves both chemical and electrical parts
.
This communication occurs at the point of contact between cells, called synapses
.
The process consists of two basic steps
.
First, the sending cell secretes (releases) a chemical called a neurotransmitter [1], causing it to enter the extracellular space (the space between the sending and receiving cells).
The neurotransmitter then diffuses to the receiving cell, binds to specific receptors on its cell membrane, and triggers ion flow across the cell membrane, which in turn prompts electrical activity in the receiving cell (Figure 1).
Figure 1: Information transfer
between synapses of nerve cells.
Communication between nerve cells occurs at specific contact locations
called synapses.
First, presynaptic nerve cells (cell A, the signaling side) release a chemical, called a neurotransmitter, into the spaces
between cells.
The neurotransmitter passes through the gap and binds
to postsynaptic nerve cells (cell B, the signal receiver).
Next, ion channels on the postsynaptic cell membrane open and ions begin to flow through the channel, producing electrical signals called peak potentials (inside the blue circle on the right).
03 My RNA research path:
Ions and membrane channels
of nerve cells Most of the electrical activity in the brain is produced by four ions, three of which are positively charged (sodium- Na+, potassium-K+ and calcium-Ca2+), A negatively charged (chlorine-Cl-).
Ions can move in and out of the cell through the nerve cell membrane, changing the potential on both sides of the cell membrane
.
Rapid changes in potential create peak potentials, which are fundamental to the "language" used to communicate between nerve cells (Figure 1).
You can think of the peak potential as the "lightning" that occurs in active nerve cells, except that it is very short (1 millisecond, or thousandths of a second) and tiny (0.
1 volts, or 100 millivolts).
So, how do these ions cross nerve cell membranes? How do neurotransmitters translate into the electrical activity of cells? When I started working in this field, no one had yet understood the mechanism by
which ions crossed nerve cell membranes.
There must be a pathway on the cell membrane to allow ions to pass through, otherwise the signal
cannot be transmitted.
In order to carry out the research, my colleague Professor Erwin Nell [2] and I developed a special experimental technique, and we found that ions with chemical gradients can indeed pass through the cell membrane through small "holes" in the cell membrane
.
These "pores" are actually protein structures that act as channels that connect the outside and inside of the cell, called ion channels (Figure 2).
We found that ion channels turn on and off
quickly when receiving neurotransmitters.
The opening and closing of specific ion channels (e.
g.
, Na+ ions or K+ ion channels) causes the corresponding ions to cross the cell membrane, thereby changing the transmembrane potential and causing the receiving cell to produce a peak potential
.
to Ion Channel Discovery: Patch-Clamp Technology
When Professor Nell and I began studying ion flow in nerve cells, we thought of two possible ion transport mechanisms
。
.
The tip of the pipette is about one micron (thousandths of a millimeter) in diameter (Figure 3A) and has a galvanometer at the other end for measuring the current
.
We press the tip of the pipette firmly against a small piece of cell membrane and apply suction so that the pipette tip and membrane are in close contact to ensure that ions are not lost
.
Because the diaphragm is small, we have also succeeded in reducing background noise to better record the flow of ions through the ion channels
.
05My path to RNA research
When the neurotransmitter binds to the membrane receptor, the ion channel opens rapidly in a stepped pattern, allowing tiny currents of several picoamperes to pass through the cell membrane (10-12 amperes for 1 picoampere) [2-4].
After the signal-receiving cell releases the neurotransmitter, the ion channel closes (Figure 3B).
Figure 3 measures the current
through the membrane ion channel.
(A) Patch-clamp technology
.
The glass tip of the pipette fits
snugly against a small cell membrane with ion channels (purple, see enlarged image).
When the neurotransmitter in the pipette binds to the cell membrane, it causes ions to pass through an open channel
.
The galvanometer of the pipette measures the current
flowing through the ion channel.
(B) Measure the current
through a single ion channel on the diaphragm.
When membrane receptors bind or release neurotransmitters, ion channels open or close (see Figure 1).
The background noise current (green)
can be measured when the ion channel is closed.
When the ion channel is opened, a rapidly downward stepped current (orange) is observed (image adapted from the study by Nell and Sackman [2]
).
We found that ion channels open or close for only a few milliseconds (a millisecond is a thousandth of a second).
Because neurotransmitter molecules bind to ion channels at random, respectively, the length of time for which the ion channels remain open or closed, and the time intervals at which they switch between the two states vary
.
As shown in Figure 3B, the amplitude of the current flowing through an open ion channel is fairly stable
.
By measuring the tiny current flowing through the diaphragm and making calculations, we estimate that approximately 10,000 ions pass through the diaphragm
every millisecond.
This tells us that the opening of ion channels is the mechanism by which ions cross the cell membrane, not through the transport molecules! Transport molecules cannot transport ions across cell membranes at such a fast rate
.
This is an important discovery that confirms the existence and function of ion channels, showing that ion channels are the fundamental mechanism
by which nerve cells generate peak potential and other electrical activities.
In other "excitable" tissues, such as peripheral muscles and the heart, ion channels are also responsible for generating electrical activity
.
In addition, understanding the function of membrane ion channels is an important topic, as many neurological (as well as cardiac and other tissue) disorders are caused by ion channel dysfunction, which is collectively referred to as ion channel disease
.
for young readers: My mentor, Professor Bernard Katz, was the
1970 Nobel Prize winner in physiology or medicine.
The first thing I'll tell you is exactly the most important thing I've learned from him: you need to be very picky about experimental results and always ready for new discoveries that may negate your previous discoveries — unpleasant
as they may be.
I also pass on this to my students, teaching them to be critical of
their findings.
Especially in biological tissues, many effects are uncontrollable and must be taken into account
when experimenting.
So when students make new discoveries, I advise them not to make them public for a while, but to repeat the experiment over and over again to see if they can get consistent results
.
Only publish the results when you are absolutely sure that they are correct
.
On the level of life concept, I think that a good life will make people think, have the opportunity to follow curiosity and make new discoveries
.
Some people may think that a good life means making a lot of money or being recognized by others, and that's perfectly fine
.
I think becoming a scientist is the best option, but only if you are interested in the natural sciences and have the urge to discover new things
.
If you just think the profession of scientist is cool, then don't go down this path and choose another profession that excites you and is full of passion
.
in the brain.
e.
, neurotransmitters) pass from the cell that sends the signal (presynaptic cells) to the cells that receive the signal (postsynaptic cells).
of information between nerve cells.
of the particles.
with a positive or negative charge.
of the cell membrane.
Positively charged ions flow
from high potential to low potential.
in the concentration of substances in different regions.
In our case, ions on both sides of the cell membrane "follow" a chemical gradient, moving from the side with a high concentration to the side
with a low concentration.
.
1971.
Quantal mechanism of neural transmitter release.
Science.
173:123–6.
, Hamill, O.
P.
, and Sakmann, B.
1987.
Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurones.
J.
Physiol.
385:243–86.
: Bert Sakmann
: In September last year, the Frontiers for Young Minds journal website (hereinafter referred to as "FYM") launched a collection of scientific articles written by five Nobel Prize winners specifically for teenagers, and "Mr.
Sai" was officially authorized by FYM to release Chinese translation for the first time
.
This November, the FYM Nobel Prize Collection series was updated with five new articles
written by Nobel laureates for curious brains around the world.
"Mr.
Sai" is exclusively authorized by FYM and will translate these five articles and share them with Chinese readers
.
Currently, the collection includes the following articles: "Nobel Laureates Interpreting Gravitational Waves:
A New Window into the Universe" – 2017 Nobel Laureate in Physics Barry Barish
Like all articles published at Frontiers for Young Minds, the authors of the Nobel Prize collection need to rewrite the article in children's language, and then a review report from a young reviewer aged 8-15 years old before the article can be published to ensure that the article is easy to understand and interesting
.
The Nobel Prize Collection series will continue to be updated with the aim of developing this valuable educational resource to inspire young people while encouraging the building
of analytical thinking and imagination.
author
Translated by Bert Sakmann (Professor at the Max Planck Institute for Neurobiology, winner of the 1991 Nobel Prize in Physiology and Medicine).Li Juan
ProofreadingMaya Blue
The normal work of the brain is inseparable from the communication
between nerve cells.
Interpreting the "language" of nerve cells is key
to our understanding of the brain.
How are signals sent by one nerve cell captured by another cell? What kind of electrophysiological activity will occur? Combined with the scientific experiments I have done, I will introduce readers to the most basic component of the brain's electrophysiological activity, ion channels, and help you better understand how nerve cells communicate
.
The discovery of ion channels has laid the foundation for understanding the electrophysiological activity of the brain and other organs, such as the heart, and has provided new insights
into drug development to treat electrical activity-related diseases such as epilepsy and arrhythmias.
My RNA research path
is how cells communicate with each other
Cells are the basic building blocks of
life.
The individual cells of our body are both independent functions and part of
organisms that need to work together, such as the brain and heart.
.
The presence of cell membranes allows each cell to maintain a stable internal environment to perform its own special functions
.
However, most cells are part of the organ and cannot exist
in isolation.
To function properly, it is necessary to communicate with other cells, especially nerve cells
.
So, how do cells separated by cell membranes communicate? There are many ways to do this, the most common of which is that one cell sends a chemical messenger substance [1], and another cell receives the messenger and responds
accordingly.
This approach is also a key point
discussed in this article.
: communication
between nerve cells, nerve cells are the basic components of the brain, and their communication relies on "electrical language"
.
At each given moment, each nerve cell exhibits specific electrical activity, producing a set of brief electrical impulses called peak potentials
.
In the process of brain activity, the entire network of nerve cells will constantly produce peak potentials, like playing a harmonious "electric symphony"
.
Such electrical activity is closely related to
our rich actions, thoughts, feelings, and memories.
In order to play this "electric symphony", how do nerve cells communicate with each other? In fact, communication between nerve cells is much more complex than communication between other cell types because it involves both chemical and electrical parts
.
This communication occurs at the point of contact between cells, called synapses
.
The process consists of two basic steps
.
First, the sending cell secretes (releases) a chemical called a neurotransmitter [1], causing it to enter the extracellular space (the space between the sending and receiving cells).
The neurotransmitter then diffuses to the receiving cell, binds to specific receptors on its cell membrane, and triggers ion flow across the cell membrane, which in turn prompts electrical activity in the receiving cell (Figure 1).
Figure 1: Information transfer
between synapses of nerve cells.
Communication between nerve cells occurs at specific contact locations
called synapses.
First, presynaptic nerve cells (cell A, the signaling side) release a chemical, called a neurotransmitter, into the spaces
between cells.
The neurotransmitter passes through the gap and binds
to postsynaptic nerve cells (cell B, the signal receiver).
Next, ion channels on the postsynaptic cell membrane open and ions begin to flow through the channel, producing electrical signals called peak potentials (inside the blue circle on the right).
03 My RNA research path:
Ions and membrane channels
of nerve cells Most of the electrical activity in the brain is produced by four ions, three of which are positively charged (sodium- Na+, potassium-K+ and calcium-Ca2+), A negatively charged (chlorine-Cl-).
Ions can move in and out of the cell through the nerve cell membrane, changing the potential on both sides of the cell membrane
.
Rapid changes in potential create peak potentials, which are fundamental to the "language" used to communicate between nerve cells (Figure 1).
You can think of the peak potential as the "lightning" that occurs in active nerve cells, except that it is very short (1 millisecond, or thousandths of a second) and tiny (0.
1 volts, or 100 millivolts).
So, how do these ions cross nerve cell membranes? How do neurotransmitters translate into the electrical activity of cells? When I started working in this field, no one had yet understood the mechanism by
which ions crossed nerve cell membranes.
There must be a pathway on the cell membrane to allow ions to pass through, otherwise the signal
cannot be transmitted.
In order to carry out the research, my colleague Professor Erwin Nell [2] and I developed a special experimental technique, and we found that ions with chemical gradients can indeed pass through the cell membrane through small "holes" in the cell membrane
.
These "pores" are actually protein structures that act as channels that connect the outside and inside of the cell, called ion channels (Figure 2).
We found that ion channels turn on and off
quickly when receiving neurotransmitters.
The opening and closing of specific ion channels (e.
g.
, Na+ ions or K+ ion channels) causes the corresponding ions to cross the cell membrane, thereby changing the transmembrane potential and causing the receiving cell to produce a peak potential
.
Figure 2: Ion channels
in nerve cell membranes.
Ion channels (purple) are "pores" made of proteins located on
nerve cell membranes.
Ion channels on postsynaptic cells (see Figure 1) are normally turned off (left panel) and open when receiving neurotransmitters released by presynaptic cells (right panel).
The opening of membrane ion channels enables ions (orange spheres) to cross the membrane, which is the basic mechanism
by which nerve cells generate electrical activity.
to Ion Channel Discovery: Patch-Clamp Technology
When Professor Nell and I began studying ion flow in nerve cells, we thought of two possible ion transport mechanisms
。
The first possible mechanism involves transporting molecules
.
Specific transporter molecules in the membrane are able to "trap" ions, transporting them from outside the cell to the inside for release
.
We already know that this mechanism exists in other activities of the body, such as during energy production, where nutrient molecules can cross cell membranes
through transport molecules.
A second possible mechanism, later confirmed by our experiments, is the presence of specific ion channels in the cell membrane that can be turned on or off
.
When the channel is opened, ions can flow on both sides of the membrane, connecting the cell's external environment with its internal environment (Figure 2).
To determine whether this mechanism is responsible for transporting ions in and out of cells when peak potentials are generated, we need to investigate
the electrical activity generated when ions pass through individual ion channels.
To do this, we need to isolate a very small area of the nerve cell membrane to measure the current through a single ion channel in that region, which is called a diaphragm
.
If ion channels do exist, we should be able to measure specific patterns of electrical activity corresponding to the opening and closing of ion channels, which is different
from the mode of electrical activity of the first possible mechanism.
In order to measure the current, we had to overcome two main challenges
.
First, we must measure all ions passing through the diaphragm channel without missing
anything.
This is difficult because the recording device must fit snugly with the membrane, otherwise ions may be lost
from the side of the detection device.
Therefore, we need to ensure that all through-membrane ions flow through the detector
.
The second challenge is to distinguish between the two currents
flowing through the nerve cell membrane.
The constant presence of steady electrical activity on nerve cell membranes is called background noise, which is different
from the electrical activity associated with ion flow.
We had to find a way to reduce background noise so that the current of individual ion channels was not masked
.
.
The tip of the pipette is about one micron (thousandths of a millimeter) in diameter (Figure 3A) and has a galvanometer at the other end for measuring the current
.
We press the tip of the pipette firmly against a small piece of cell membrane and apply suction so that the pipette tip and membrane are in close contact to ensure that ions are not lost
.
Because the diaphragm is small, we have also succeeded in reducing background noise to better record the flow of ions through the ion channels
.
05My path to RNA research
The current flowing through the ion channel
We found that when neurotransmitters are not present in the environment, no current passes through ion channels and only slight background noise is observed (Figure 3B).When the neurotransmitter binds to the membrane receptor, the ion channel opens rapidly in a stepped pattern, allowing tiny currents of several picoamperes to pass through the cell membrane (10-12 amperes for 1 picoampere) [2-4].
After the signal-receiving cell releases the neurotransmitter, the ion channel closes (Figure 3B).
Figure 3 measures the current
through the membrane ion channel.
(A) Patch-clamp technology
.
The glass tip of the pipette fits
snugly against a small cell membrane with ion channels (purple, see enlarged image).
When the neurotransmitter in the pipette binds to the cell membrane, it causes ions to pass through an open channel
.
The galvanometer of the pipette measures the current
flowing through the ion channel.
(B) Measure the current
through a single ion channel on the diaphragm.
When membrane receptors bind or release neurotransmitters, ion channels open or close (see Figure 1).
The background noise current (green)
can be measured when the ion channel is closed.
When the ion channel is opened, a rapidly downward stepped current (orange) is observed (image adapted from the study by Nell and Sackman [2]
).
We found that ion channels open or close for only a few milliseconds (a millisecond is a thousandth of a second).
Because neurotransmitter molecules bind to ion channels at random, respectively, the length of time for which the ion channels remain open or closed, and the time intervals at which they switch between the two states vary
.
As shown in Figure 3B, the amplitude of the current flowing through an open ion channel is fairly stable
.
By measuring the tiny current flowing through the diaphragm and making calculations, we estimate that approximately 10,000 ions pass through the diaphragm
every millisecond.
This tells us that the opening of ion channels is the mechanism by which ions cross the cell membrane, not through the transport molecules! Transport molecules cannot transport ions across cell membranes at such a fast rate
.
This is an important discovery that confirms the existence and function of ion channels, showing that ion channels are the fundamental mechanism
by which nerve cells generate peak potential and other electrical activities.
In other "excitable" tissues, such as peripheral muscles and the heart, ion channels are also responsible for generating electrical activity
.
In addition, understanding the function of membrane ion channels is an important topic, as many neurological (as well as cardiac and other tissue) disorders are caused by ion channel dysfunction, which is collectively referred to as ion channel disease
.
For our discovery of membrane ion channels and their functions, my colleague Professor Erwin Nell and I won the 1991 Nobel Prize
in Physiology and Medicine.
for young readers: My mentor, Professor Bernard Katz, was the
1970 Nobel Prize winner in physiology or medicine.
The first thing I'll tell you is exactly the most important thing I've learned from him: you need to be very picky about experimental results and always ready for new discoveries that may negate your previous discoveries — unpleasant
as they may be.
I also pass on this to my students, teaching them to be critical of
their findings.
Especially in biological tissues, many effects are uncontrollable and must be taken into account
when experimenting.
So when students make new discoveries, I advise them not to make them public for a while, but to repeat the experiment over and over again to see if they can get consistent results
.
Only publish the results when you are absolutely sure that they are correct
.
On the level of life concept, I think that a good life will make people think, have the opportunity to follow curiosity and make new discoveries
.
Some people may think that a good life means making a lot of money or being recognized by others, and that's perfectly fine
.
I think becoming a scientist is the best option, but only if you are interested in the natural sciences and have the urge to discover new things
.
If you just think the profession of scientist is cool, then don't go down this path and choose another profession that excites you and is full of passion
.
- Definition of nouns:
NERVE CELLS
The main cells that make up the brain and produce electrical activityin the brain.
SYNAPSE SYNAPSES
At the point of contact between two nerve cells, there is a narrow gap through which chemicals (i.e.
, neurotransmitters) pass from the cell that sends the signal (presynaptic cells) to the cells that receive the signal (postsynaptic cells).
NEUROTRANSMITTER NEUROTRANSMITTER
A chemical substance that is released and absorbed by nerve cells to enable the transmissionof information between nerve cells.
DIFFUSION diffusion
The non-directional spontaneous motionof the particles.
ION ion
Particleswith a positive or negative charge.
ELECTRICAL POTENTIAL potential
It arises between two points with different electrical charges, in our case on both sidesof the cell membrane.
Positively charged ions flow
from high potential to low potential.
CHEMICAL GRADIENT
Differencesin the concentration of substances in different regions.
In our case, ions on both sides of the cell membrane "follow" a chemical gradient, moving from the side with a high concentration to the side
with a low concentration.
ION CHANNEL ion channel
A small hole in the cell membrane, made of proteins, opens to allow ions to enter or flow out of the cell.
Translation Checklist:
Bert Sakmann
Peak potential spike
Erwin Neher
Patch clamp
Channelopathy
Bernard Katz
Max Planck Institute for Neurobiology
Ludwig Maximilian University of Munich- References:
1971.
Quantal mechanism of neural transmitter release.
Science.
173:123–6.
[2] Neher, E.
, and Sakmann, B.
1992.
The patch clamp technique.
Sci.
Am.
266:44–51.
[3] Hamill, O.
P.
, and Sakmann, B.
1981.
Multiple conductance states of single acetylcholine receptor channels in embryonic muscle cells.
Nature.
294:462–4.
, Hamill, O.
P.
, and Sakmann, B.
1987.
Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurones.
J.
Physiol.
385:243–86.
Thanks:
Thanks to Noa Segev for the interview and co-writing
.
About the author
: Bert Sakmann
Bert Sakmann is a professor
at the Max Planck Institute for Neurobiology in Munich, Germany.
Professor Sackmann initially studied for a doctorate
in medicine at the Ludwig-Maximilians-Universität München.
During his preclinical research, his research spanned the fields of
biophysics and neurophysiology.
He became interested in neuroscience, especially the mechanisms by which the brain produces and transmits electrical signals
.
To this end, Professor Sackman transferred to University College London in 1971 to be mentored
by Professor Bernard Katz.
(Professor Katz won the 1970 Nobel Prize
in Physiology or Medicine for his discovery of the workings of neurotransmitters in nerve cells.
) ）
In 1974, Prof.
Sackmann joined the Department of Neurobiology at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, where he met collaborator Professor Erwin Nell, who together developed the patch-clamp technique and discovered single ion channels, for which he was awarded the 1991 Nobel Prize
in Physiology and Medicine.
”
About Frontiers for Young Minds
Frontiers for Young Minds, founded in 2013, is a scientific journal for children founded by Frontiers Publishing House in Switzerland, and it is also a pure public welfare project
that Frontiers has spent many years cultivating.
It operates in exactly the same way as a scientific journal, designed to nurture children's scientific thinking from the teenage age and provide opportunities
to communicate with world-class scientists.
To date, 5,250 young reviewers have participated in the review, and 790 scientific mentors have guided their review process
.
Frontiers for Young Minds' more than 1,000 articles have been viewed and downloaded more than 27 million times and are available
in English, Hebrew and Arabic.
The journal's editorial board currently consists of
scientists and researchers from more than 64 countries.
Frontiers for Young Minds' content encompasses astronomy and physics, biodiversity, chemistry and materials, the Earth and its resources, human health, mathematics, neuroscience and psychology — as well as upcoming engineering and technology-related disciplines
.
While the journal's readers are teenagers, all research published in Frontiers for Young Minds is based on solid evidence-based scientific research
.
saixiansheng@zhishifenzi.
com
