BIOPOTENTIALS

Khon Huynh
School of Biomedical Engineering
Research Center for Infectious Diseases
International University – VNUHCM
hckhon@hcmiu.edu.vn

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Who am I?
Huynh Chan Khon, A/Prof. Dr.
Lab on a chip & Biosensor (A1.210)
Lecturer – School of Biomedical Engineering
Research Center for Infectious Diseases
International University – VNUHCM
Office: A1-405
Contact: hckhon@hcmiu.edu.vn
Office hour: by appointment via email

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My background

PhD Degree in Natural Science

Researcher at Heinrich-Pette-Institute
(Structural Biology) (2012)
Leibniz Institute for Experimental Virology (2019-2020)
University of Dusseldorf, Germany

journals.physiology.org

Protein structure - Function Microfluidics / Lab on a chip /

Point of Care Testing
 Current research projects
Automated POCD Vessel on a chip for Arterial Sars-CoV2 rapid Ag
device, sample-to-result Thrombosis modeling detection from Saliva

We are recruiting researchers,

under-,gra-, post-gradute students
Email to hckhon@hcmiu.edu.vn 4
Biopotentials

electric eels Anglerfish (Cá lồng đèn)

(cá chình điện)

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Content
 Review of membrane structure and permeability
 Biopotentials: resting potential and action potential
 Action potential propagation
 Synaptic neural transmission
 Example of Biopotential signal

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The cell membrane
Membrane Permeability
 Membrane structure results in selective permeability
 A cell must exchange materials with its surroundings,
a process controlled by the plasma membrane

 Small molecules (polar or nonpolar) cross easily

(hydrocarbons, hydrophobic molecules, CO2, O2)
 Hydrophobic core prevents passage of ions, large
polar molecules
Permeability of the Lipid Bilayer
 Hydrophobic molecules
Are lipid soluble and can pass through the membrane
rapidly

 Polar molecules
Do NOT cross the membrane rapidly
Transport Proteins
Transport proteins
Allow passage of hydrophilic substances
across the membrane
Passive Transport

 Passive transport is diffusion of a substance across a

membrane with no energy investment
 CO2, H2O, and O2 easily diffuse across plasma
membranes
 Diffusion of water is known as Osmosis
Facilitated Diffusion & Proteins
Channel proteins
Provide corridors that allow a specific molecule or
ion to cross the membrane
EXTRACELLULAR
FLUID

Channel protein
Solute
CYTOPLASM
A channel protein (purple) has a channel through which
water molecules or a specific solute can pass.
Facilitated Diffusion & Proteins
 Gate channel
Active Transport
Na+/K+ Pump
 Pump Na+ out, K+ into cell
Biopotentials

electric eels Anglerfish (Cá lồng đèn)

(cá chình điện)

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Luigi Galvani (1737 – 1798,
Bologna - Italia)
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18
Resting potential

+ + + + + + + + + + + + + + + + + +

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Resting potential
 A resting potential exists between the internal cell
surface and the external one (about -50mV - -94mV)
 Resting potentials has two characteristics:
◼ The inner side of the membrane is charged
electronegatively with respect to the outer one
◼ Resting potentials change very slowly over time and
dependent on cellular function

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Action potential
 Appear when cells and tissues perform functions
 There is a change in polarity (the inside is positive,
the outside is negative)
 Only appear when cells are excited, and the
stimulus intensity reaches the threshold
 Prolonged for short periods, time scales depends on
cell types (nerve and muscle cells 1msec, heart muscle
150-300 msec…)
 Have the ability to propagate 21
Waveform of the action potential

Within a short time,

cell try to be back in
resting state

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Origin of biopotentials
 Biopotentials are actually ionic voltages produced as
a result of the electrochemical activity of cells
 These ionic voltages are converted into electrical
voltages
 Biopotentials as monitoring signals are for various
functions, associated with nerve conduction, brain
activity, heartbeat, muscle activity (excitable cells) …

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Mechanism of biopotential
 Sodium-Potassium Pump
 Diffusion
 Electrical gradient

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The cell membrane
The cell membrane acts as a selective
filter, allowing the free movement of some
molecules across it while tightly controlling
the movement of others. Passage of a
specific substance across the membrane
depends on multiple factors including its
electric charge, molar mass and the
polarity of the molecule.
uncharged substances, like O2, CO2,
urea, alcohol and glucose, can move freely
as their concentration gradients allow.
Charged substances such as K+, Na+, Cl–
ions, cannot easily diffuse through the cell
membrane. Hence, will utilise ion channels.

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Ion Movement
There are three factors that can induce the movement of the ions
through ion channels:
• The concentration gradient – a difference in concentration of the
ion on the two sides of the membrane. Ions would cross the
membrane from a compartment with a higher concentration to the
compartment with a lower concentration.
• The electrical gradient – an electrical potential difference across
the membrane defined as the electrical potential value inside the cell
relative to the extracellular environment. Positive ions will be
attracted to negative electrical potential and repelled from positive
electric potential, and vice versa.
• Active Transport.

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Potassium
•The concentration gradient – The
intracellular concentration of potassium
greatly exceeds the extracellular
concentration (~130mmol/L vs ~4mmol/L).
Thus, potassium ions will tend to exit the
cell according to the concentration
gradient.
•The electrical gradient – As positively
charged K+ ions are released, the charge of
the intracellular space becomes relatively
negative. Hence, some K+ ions are
attracted back towards the intracellular
space, despite the concentration gradient
leading them in the opposite direction.

two “streams” containing K+ ions

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Bernsteins Hypothesis
 In 1902, Julius Bernstein proposed the first satisfactory
hypothesis for generation of the resting potential.
 Bernstein knew that the inside of cells have high K+ and low
Na+ concentrations and that the extracellular fluid has low K+
and high Na+ concentrations.
 cells are highly permeable to K+ but not very permeable to
other ions.
Bernstein therefore suggested that the resting potential could be
predicted simply by applying the Nernst equilibrium equation for
potassium
Theo Bernstein, ở trạng thái tĩnh, màng chỉ thấm với K+ mà không thấm với Na+, Cl-, và Lực hút
tĩnh điện đã giữ các ion lại ở màng và làm cho màng bị phân cực 1 cách bền vững.
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Equilibrium Potential
 At the equilibrium potential, the rate at which ions leave by concentration
gradient is equal to the rate at which ions enter via the electrochemical
gradient.
 Importantly, in a cell where only one type of ion can cross the membrane,
the resting membrane potential will equal the equilibrium potential for that
particular ion.

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The Science of Biology
– Sadava 2012

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 While the Nernst equation for potassium
provides a good approximation, the calculation
of resting membrane potential is slightly more
complicated because it is not the only ion
involved
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 For a typical neuron at rest,
pK : pNa : pCl = 1 : 0.05 : 0.45

Với các điều kiện:

Màng tế bào có tính chất đồng nhất và điện trường
ở đó không đổi.
Dung dịch điện ly được coi là lý tưởng
Chỉ có các ion hoá trị 1 tham gia vào việc hình
thành điện thế nghỉ
Môi trường ở 2 phía của màng rộng vô tận.

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Membranes Can Be Depolarized or Hyperpolarized

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Graded changes in membrane potential can
integrate information
 Flow of ionic electric current along plasma
membranes can only extend over short distances, it
can cause graded changes in membrane potentials
locally.
 A graded membrane potential is a change from the
resting potential due to chemical or mechanical
influences on ion channels.
 Means of integrating inputs to a cell → membrane
response (depolarization or hyperpolarization)

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Sudden changes in Na+ and K+
channels generate action potentials

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Mechanism behind action potential
When membrane stimulation exceeds a threshold, action potential occurs:
1. Sodium and potassium ionic permeabilities of the membrane change
2. Sodium ion permeability increases very rapidly at first, allowing sodium ions to
flow out->in, inside more (+)
3. The more slowly increasing postassium ion permeability allows potassium ions
to flow in->out, returning membrane potential to its resting value
4. While at rest, the Na-K pump restores the ion concentrations to their original
values

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NEURONS (NERVE CELLS)
Thân tế bào

Depending on the type

of neuron, axons greatly
vary in length - many are
just a millimetre or so, but
the longest ones, such as
those that go from the
Đuôi gai
brain down the spinal cord,
can extend for more than a
metre.
Sợi trục

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 Cấu tạo tế bào neuron
•Thân tế bào (còn gọi là Soma): là chỗ phình to của nơ-ron, bao gồm nhân tế bào, thể lưới nội chất, ty
thể, ribosom, lysosom, bộ máy Golgi, tơ thần kinh, ống siêu vi và các bào quan khác. Nơ-ron chứa 70 -
80% là nước, vật chất khô có khoảng 80% protein và 20% lipid. Thể tích của tế bào khoảng 600 -
70.000 µm³. Thân nơ-ron cung cấp dinh dưỡng cho nơ-ron, có thể phát sinh xung động thần kinh và có
thể tiếp nhận xung động thần kinh từ nơi khác truyền tới nơ-ron.
•
•Đuôi gai: là các tua ngắn phát triển từ thân tế bào. Mỗi nơ-ron đều có nhiều đuôi gai, mỗi đuôi gai
được chia thành nhiều nhánh, có chức năng tiếp nhận các xung thần kinh từ tế bào khác, truyền chúng
tới thân tế bào (tín hiệu hướng tâm). Tác động của các xung này có thể là kích thích hoặc ức chế.

•Sợi trục (còn gọi là axon): là sợi thần kinh đơn dài, làm nhiệm vụ truyền tín hiệu từ thân tế bào tới tế
bào thần kinh khác hoặc tới tế bào cơ. Đường kính của các sợi trục thường có kích thước khác nhau,
dao động từ từ 0,5 μm – 22 μm. Dọc sợi trục được bao bọc bởi một lớp vỏ myelin, tạo thành bởi các tế
bào Schwann. Bao myelin không liền mạch mà được chia thành từng đoạn. Giữa các bao myelin là các
eo Ranvier. Khoảng cách giữa 2 eo Ranvier khoảng 1,5 – 2 mm. Còn diện tích tiếp xúc giữa các nhánh
nhỏ phân từ cuối sợi trục của nơ-ron này với sợi nhánh của nơ-ron khác hoặc các cơ quan thụ cảm
được gọi là Synapse (khớp thần kinh).
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Action potential propagation
Action potential propagation

Action Potentials
Travel along Axons
Action
potentials
jump along
myelinated
axons
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Action potential propagation

Ranvier node (eo Ranvier)

https://www.youtube.com/watch?v=oa6rvUJlg7o
https://www.youtube.com/watch?v=jolNFDo2nH0 (VN)
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https://www.youtube.com/watch?v=tOTYO5WrXFU (EN)
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https://teachmephysiology.com/nervous-system/synapses/action-potential/
Action potential propagation in
(non)myelinated nerves
 Nonmyelinated nerves  Myelinated nerves
Continuous propagation Saltatory propagation
Slow and decrease in (jumping)
speed Consume less energy
Consumes lot of energy Control of muscle activity
Function: vascular
contraction, bladder,
digestion…

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Nerve impulse transmission
Neurons communicate with each other and
with other cells through structures called
synapses. At the synapse, the terminal of a
presynaptic cell comes into close contact
with the cell membrane of a postsynaptic
cell.

A synapse is a combination of:

•Presynaptic endings – which contain the
neurotransmitters (chemical messengers).
•Synaptic clefts – which is the gap
between the two neurons.
•Postsynaptic endings – which contains 20-40nm

the sites for receptors (molecules which

receives signals for a cell).
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Synapse types:
 Classification by structure
Depending on the relationship between the two components of the cell
that makes up the synapse, it has a different name:
presynaptic
terminal makes a
synaptic
connection with
the cell body of a
presynaptic terminal
postsynaptic
makes a synaptic
neuron
connection with the
dendrite of a
postsynaptic neuron

presynaptic terminal
makes a synaptic
connection with the axon
of a postsynaptic neuron

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Classification by mechanism of action: chemical synapse and
electrical synapse

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 There are two fundamentally different types of synapses:
• In a chemical synapse, electrical activity in the presynaptic neuron is converted (via the
activation of voltage-gated calcium channels) into the release of a chemical called a
neurotransmitter that binds to receptors located in the plasma membrane of the postsynaptic
cell. The neurotransmitter may initiate an electrical response or a secondary messenger
pathway that may either excite or inhibit the postsynaptic neuron. Chemical synapses can be
classified according to the neurotransmitter released: glutamatergic (often excitatory),
GABAergic (often inhibitory), cholinergic (e.g. vertebrate neuromuscular junction), and
adrenergic (releasing norepinephrine). Because of the complexity of receptor signal
transduction, chemical synapses can have complex effects on the postsynaptic cell.
• In an electrical synapse, the presynaptic and postsynaptic cell membranes are connected by
special channels called gap junctions that are capable of passing an electric current, causing
voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell. The
main advantage of an electrical synapse is the rapid transfer of signals from one cell to the
next.

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50
Acetylcholine Receptors ACh
receptors are chemically gated ion
channels found in the motor end
plate and other types of
postsynaptic membranes. When
one of these receptors binds ACh,
its channel pore opens and Na+
moves into the postsynaptic cell,
depolarizing its membrane. The
enzyme acetylcholinesterase
(AChE) breaks down ACh in the
synapse, closing the channel. The
breakdown products (acetate and
choline) are then taken up by the
presynaptic membrane and
resynthesized into more ACh

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Synapses can be fast or slow
 Ionotropic receptors are themselves ion channels. Neurotransmitter
binding to an ionotropic receptor causes a direct change in ion movement
across the plasma membrane of the postsynaptic cell. These proteins enable
fast, shortlived responses.
 Metabotropic receptors are not ion channels,
but they induce signaling cascades in the
postsynaptic cell that secondarily lead to
changes in ion channels. Postsynaptic cell
responses mediated by metabotropic receptors
are generally slower and longer-lived than
those induced by ionotropic receptors.

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Electrical synapses are fast but do
not integrate information well

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Electrical synapses are less common in the
nervous systems of vertebrates than are chemical
synapses
First, electrical continuity between neurons does
not allow temporal summation of synaptic
inputs.
Second, an effective electrical synapse requires a
large area of contact between the presynaptic and
postsynaptic cells.
Third, electrical synapses cannot be inhibitory.
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What happens at the level of complete
tissues?
 We have a combination of several neurons or several
electrically connected tissues. The description of the
conduction is no more made at the level of the single
cell transmission of the pulse.
 Biopotentials signals, such as EEG, ECG, and EMG,
are generated from volume conduction of currents
made by collections of electrogenic cells. EEG, is the
electrical potential induced from collective activities
of large number of neurons in the brain. ECG is
resulted from action potentials of cardiac muscle
cells… 55
 ECG represents the sum of the action
potentials of millions of cardiomyocytes
Electrocardiogram (ECG or EKG)
 An electrocardiogram (ECG or EKG) is a register of the heart's
electrical activity.

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57
The different ECG waves
The P wave is the result of the atrial depolarization. This depolarization starts in the SA (sinoatrial)
node. The signal produced by pacemaker cells in the SA node is conducted to the right and left atria.
Normal atrial repolarization is not visible on the ECG (but can be visible during atrial infarction and
pericarditis).
The QRS complex is the average of the depolarization waves of the inner (endocardial) and outer
(epicardial) cardiomyocytes. As the endocardial cardiomyocytes depolarize slightly earlier than the
outer layers, a typical QRS pattern occurs (figure).
The T wave represents the repolarization of the ventricles. There is no cardiac muscle activity during
the T wave.
One heart beat consists of an atrial depolarization --> atrial contraction --> p-wave, ventricular
depolarization --> ventricular contraction --> ORS-complex and the resting phase (including the
repolarization during the T-wave) between two heart beats.
Have a look at this [animation of the heart cycle]
The origin of the U wave is unknown. This wave possibly results from "afterdepolarizations" of the
ventricles.
The letters "Q", "R" and "S" are used to describe the QRS complex
•Q: the first negative deflection after the p-wave. If the first deflection is not negative, the Q is absent.
•R: the positive deflection
•S: the negative deflection after the R-wave
•Small print letters (q, r, s) are used to describe deflections of small amplitude. For example: qRS =
small q, tall R, deep S.
•R`: is used to describe a second R-wave (as in a right bundle branch block) 58
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 1. Cấu tạo và chức năng chính của tim
Thông thường, tim người được chia thành 4
phần, bao gồm:
• Ở nửa trên: tâm nhĩ trái và tâm nhĩ phải. Đặc
điểm chung của hai tâm nhĩ này là có thành
mỏng, được ngăn cách bởi vách liên nhĩ, nhĩ
phải nhận nhiệm vụ đưa máu đổ về từ tĩnh
mạch chủ trên và dưới xuống tâm thất phải,
nhĩ trái nhận máu trở về từ phổi đưa xuống
thất trái.
• Ở nửa dưới: tâm thất trái và tâm thất phải.
Các tâm thất thường có thành dày, được
ngăn cách bởi vách liên thất, đảm nhiệm vai
trò bơm máu vào động mạch. Tâm thất phải
bơm máu vào động mạch phổi để máu nhận
Oxy và thải khí CO2, tâm thất trái bơm máu
lên cung động mạch chủ để máu đi nuôi khắp
cơ thể. 60