Physiology 1.

1 Excitable tissues

Module 1. EXCITABLE TISSUES

1.1. EXCITATION AND EXCITABILITY OF THE NERVOUS AND MUSCULAR

TISSUES

Aims of the module

A student should know
1) How to investigate the physiological properties of excitable tissues. Irritation. Excitement
2) The structure and the functions of the membranes. Ion mechanisms of the resting
membrane potential.
3) Methods for membrane potentials registration. Action potential: the phases and its ionic
mechanisms. Local response and action potential.
4) The law "All or none".
5) Excitability during the different phases of the action potential. Refractory period.
6) Types of stimulation for excitable tissues. Correlation between threshold and excitability.
Characteristics of excitability for nerves and muscles.

Theoretical information
Transmembrane transport
The contents of a cell are separated from the surrounding extracellular fluid by a thin layer
of lipids and protein — the membrane. The classification of transmembrane transport according
to the energy required for transport include
1) passive (no energy is needed, happens according to the concentration gradient from high
level to low level of a substance) and
2) active transport (energy is required, the transport from low to high concentration of a
substance, against the concentration gradient).

Fig. 1 The types of

transport through
the membrane.
Etienne et al., 2013

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 Physiology 1.1 Excitable tissues

Fig. 2. Movement of solutes

across a typical membrane
involving membrane proteins.
Many of these membrane proteins
can be modulated by various
signals, leading to a controlled
increase or decrease in specific
solute fluxes across the
membrane.

Excitable tissues
An excitable cell reacts to stimuli by altering its membrane characteristics. There are two types of
excitable cells: nerve cells and muscle cells.
Cells under resting conditions have a potential difference across their plasma membranes, with the
inside of the cell negatively charged with respect to the outside. This potential is the resting
membrane potential.

The resting membrane potential of large nerve fibers when not transmitting nerve signals is about
−90 millivolts. That is, the potential inside the fiber is 90 millivolts more negative than the
potential in the extracellular fluid on the outside of the fiber.

The reasons for the resting membrane potentials are

1) Active Transport of Sodium and Potassium Ions Through the Membrane—The Sodium-
Potassium (Na+-K+) Pump. Na+-K+ ATPase continually transports sodium ions to the outside of
the cell and potassium ions to the inside
2) Leakage of Potassium Through the Nerve Membrane via opened K+-channels.
3) Sodium channels are closed and Na+ may not enter the cell. It stays outside the cell.

Fig. 3 Na+-K+ ATPase continually transports sodium ions to the outside of the cell and potassium
ions to the inside. Potassium leaves the cell through the K leak channels. ADP, adenosine
diphosphate; ATP, adenosine triphosphate.

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 Physiology 1.1 Excitable tissues

Nerve and muscle cells are capable of generating rapidly changing electrochemical
impulses at their membranes, and these impulses are used to transmit signals along the nerve or
muscle membranes.
Action potentials are rapid changes in the membrane potential that spread rapidly along
the membrane. Each action potential begins with a sudden change from the normal resting negative
membrane potential to a positive potential and then ends with an almost equally rapid change back
to the negative potential.
Brief, rapid, large and reversible change in resting membrane potential of an excitable cell
during which the membrane potential reverses (cell inside becomes more positive than outside) is
known as action potential.

Fig 4. Features of a
typical action potential
recorded from a nerve or
muscle cell stimulated
with an electrode. //
Boron’s Physiology

If the stimulus applied to an excitable cell

is big enough and the membrane potential comes
close to a critical voltage or threshold potential,
“rapid” voltage-gated Na+ channels are activated.
This results in increased Na+ conductance, and
Na+ moves into the cell.
If the stimulus applied to an excitable cell
is big enough and the membrane potential comes
close to a critical voltage or threshold potential,
“rapid” voltage-gated Na+ channels are activated.
This results in increased Na+ conductance, and Na+
moves into the cell.

Fig. 5. Action potential mechanisms.

If the threshold potential is not reached, this process remains a local (subthreshold)
response. Once the threshold potential is reached, the cell responds with a fast all-or-none
depolarization called an action potential.
After sodium channels are closed, restoration of the resting potential, the repolarization
phase of the action potential, begins. Voltage-gated K+ channels open and K+ moves from the cell
(Fig. 6).

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 Physiology 1.1 Excitable tissues

Fig. 6. Changes in ionic

conductance that underlie the
action potential. (Data from
Hodgkin AL, Huxley AF:
Aquantitative description of
membrane current and its
application to conduction and
excitation in nerve. J Physiol
117:500– 544, 1952.)

The threshold, amplitude, time course, and duration of the action potential depend on the
following factors:
1. The gating (opening and closing) and permeability properties of specific types of ion
channels—these properties depend on both Vm and time.
2. The intracellular and extracellular concentrations of the ions that pass through these
channels, such as Na + , K+ , Ca 2+ , and Cl –.
3. Membrane properties such as capacitance, resistance, and the geometry of the cell.

Determinants of excitability. The laws of irritation of excitable tissues.

All or none principle: Action potential will either be generated or not…no gradations
Suprathreshold stimulus will elicit same action potential as elicited by threshold stimulus.
Subthreshold stimulus will not elicit action potential.
Strength- duration curve: In the preceding section, the importance of the magnitude
(intensity) of the depolarizing stimulus emerged as a critical factor for firing of an action potential.
However, the duration of the stimulus pulse is also important. A large stimulus is effective in
triggering an action potential even at short duration, and a small stimulus may be effective at long
duration (Fig. 7). This strength-duration relationship arises because the same minimum electrical
charge necessary to excite an action potential can come from a current that is either brief but large
or prolonged but small. It is the product of strength and duration that determines excitability, and
thus these two parameters are inversely related in their effectiveness. However, regardless of the
stimulus strength, successful stimulation requires a minimum duration (vertical asymptote).
Conversely, regardless of the stimulus duration, successful stimulation requires a minimum
strength (horizontal asymptote). As the duration of a stimulus increases, the minimum intensity of
stimulation required to elicit an action potential decreases. The rheobase is the minimum intensity
of stimulation required to generate an action potential when the stimulation is of infinite duration
(i.e., the horizontal dashed line). Stimuli with an intensity greater than the rheobase require shorter
times. When the stimulus intensity is twice the rheobase, the minimum duration required to achieve
an action potential is the chronaxie.

Fig. 7. The curve represents the combination of the

minimum stimulus intensity and duration that is
required to reach threshold and to evoke an action
potential // Boron’s Physiology

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 Physiology 1.1 Excitable tissues

The law of accommodation: characterizes the rate of increase of irritation intensity that
is necessary for excitation. The lower this rate, the longer the time interval will be for excitation.
During accommodation, the tissue adapts to the action of the gradually increasing intensity of
irritation (Fig. 8).

Fig. 8. Change in the amplitude of the action

potential and the level of the critical
depolarization of the nerve with a gradual
increase in the intensity of the irritation:
membrane potential in case of the deceleration
of the increase of irritation intensity (V –
voltage applied to the inner surface of the
membrane, t - time; RP – resting potential; CD
– critical depolarization; 1-3 – action potentials;
4 – local response; 5 – membrane potential with
slowly increasing subthreshold irritation) //
Normal Physiology be K.V. Sudakov

Excitability
During an action potential, the cell remains unresponsive to further stimuli; this is called
the refractory period. In the absolute refractory period during depolarization, no other action
potential can be triggered, even by extremely strong stimuli, since Na+ channels in depolarized
membranes cannot be activated. This is followed by a relative refractory period during which
action potentials can be generated only by strong stimuli. The refractory period ends once the
membrane potential returns to its resting value (Fig. 9).
The presence of a refractory period limits the frequency with which a neuron or a muscle
cell may generate action potentials.

EXAM CHART*
*The chart should be transferred to the
notebook
Fig.9. Excitability during different phases of action
potential.
D – depolarization
R – repolarization
H –hyperpolarization
E – exaltation
AR – absolute refractory period
RR – relative refractory period

Absolutely refractory period

Period during which a 2nd action potential can not be
generated. This can be elicited from start of
depolarization to initial 1/3 of repolarization
Relative refractory period
Period during which 2nd action potential can be
generated but with stronger than normally required
stimulus.

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 Physiology 1.1 Excitable tissues

Practical tasks.
Task 1.
Read the experiment described below. Transfer the description to the notebook.
Write a conclusion and answer the questions.
Watch the demonstration of the experiment.

Experiment: Comparison of the excitability of the nerve and muscle.

To determine the excitability of the excitable tissue it is necessary to determine the minimal
amplitude of stimulus (threshold of irritation) capable to cause action potential.
Take the nerve-muscle preparation. Fix it. Stimulate the nerve with the lowest possible
stimulation. Then slowly increase the stimulation amplitude. Once you see the contraction of the
muscle, note the threshold.
Then stimulate the muscle with the slowest possible stimulation. Then slowly increase the
stimulation amplitude. Once you see the muscular contraction, note the result.
Compare the amplitude of the stimuli required for the indirect (via nerve) and direct (via
muscle) stimulation. Make a conclusion.

Fig.10. The registration of the muscular contractions after stimulation.

Fig.11. Miogram of the muscle after the A – indirect

and Б – direct stimulation. The arrows show the
time of stimulation, the numbers show the
amplitude of stimulation, V. Амп – the amplitude of
the muscular contraction.

The protocol should include

1) The title of the experiment
2) The aim of the experiment
3) The picture of the myogram after electrical stimulation.
4) The comparison between the threshold stimuli for direct and indirect stimulations.
5) The conclusion about the nerve and muscular excitability.

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 Physiology 1.1 Excitable tissues

Task 2.
Formulate and write down the definitions of the terms that characterize the mechanisms of the
penetration of substances through the cell membranes:
- Active transport
- Passive transport
- Simple diffusion
- Facilitated diffusion
- Osmosis

Task 3. Transfer the right answers into your notebook.

Definition: Resting membrane potential of the excitable cell
is____________________________________________________________________________
Specify the distribution of charges and ions on the membrane of the nerve cell, membrane potential
(MP) ___ mV.
Different concentration of ions is due to the work of the transport protein -_________________
(type).
Show the charge (+ or - ) on the external and internal surfaces of the nerve cell on the fig.12.

Fig. 12. Polarization of the nerve cell membrane in

the resting state (resting potential). Show the
charge (+ or - ) on the external and internal
surfaces of the nerve cell.

Check your knowledge.

Are you ready to answer the following exam questions?

1. Electrogenesis in excitable tissues. Methods for membrane

potentials registration. Action potential: the phases and it’s ionic
mechanisms. The law "All or none".
2. Types of stimulation for excitable tissues. Correlation between
threshold and excitability. Change of excitability during excitation:
origin. Characteristics of excitability for nerves and muscles.

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 Physiology 1.1 Excitable tissues

Literature
Theoretical material:
1. Color atlas of physiology / S. Silbernagl, A. Despopoulos. - 7 ed. - 2015.- p.472. (Thieme
Verlagsgruppe)
2. Ionkina E.G., Glazachev O.S., Vaguine Yu,.Ye. Physiology: A practical textbook for medical
students. Edited by K.V.Sudakov - Moscow: Sechenov Moscow Medical Academy, 2006. - p.172.

3. Textbook of Medical Physiology / Guyton, Arthur C., Hall John.E. - 13th Edition - p.1168.
(Elsevier Science)
3. Video Lecture Excitable tissues

Additional material:
1. Principles of Anatomy and Physiology. / Tortora Gerard J. 13th Edition- p. 1536 (Wiley)
2. Physiology / Costanzo, Linda S. - 6th edition _ 2017 - p. 528.(Elsevier Science)
3. Fundamentals of Medical Physiology. Joel Michael, Sabyasachi Sircar. - 2010. - p. 633.
(Thieme)