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3 Excitability & Excitation

• Excitable cells
- neuron, muscle, gland
• Excitability
• Excitation

Excitability is an ability or property of

generation of the action potential while
a excitable cell responds to appropriate
Excitation is a process of the AP was
Three essential parameters
regarding stimulation
 Parameters
Intensity 刺激强度
Duration 刺激作用时间
Rate of change ( in intensity )
 Terms
Threshold intensity 阈强度
Threshold stimulus 阈刺激
Subthreshold stimulus 阈下刺激
Suprathreshold stimulation 阈上

Changes of excitability
during excitation

 Absolute refractory period 绝对不应期

 Relative refractory period 相对不应期
 Supernormal period 超常期
 Subnormal period 低常期


立即接受刺激爆发另一个新的 AP 。
 不应期的长短决定了细胞在单位时间
,而 AP 的频率是可兴奋细胞接受刺激
The factors that effects on
excitability of the cell
 Resting potential-[K+]o/[K+]I.

 Threshold

 Ca2+ concentration outside of

the cells (surface charge)
§2.4 Initiation and
Propagation of the Action

Initiation of the
Action Potential
How does depolarization open
voltage-gated channels?

 There is a threshold for

generation of action potential; i.e.
small random fluctuations in the
membrane potential are not
interpreted as useful information.
Why is that?
 The stimulus might be produced by a
sensory receptor, an action potential in
nearby parts of the cell or from an
electrical current applied experimentally.

Current flowing into the cell lowers the

membrane potential towards zero.
There are two immediate effects:
1. The difference between Vm and the EK
increases – more K+ flows out of the
cell. This tends to repolarize the cell.
2. The voltage-gated Na+ channels are
opened allowing Na+ to flow down its
gradient into the cell. This tends to
produce further depolarization.
The result is determined by the
relative sizes of these two effects.
 With small depolarizations, the effect

on the IK is larger than that on INa and

the outward IK exceeds the inward INa
(Ik>INa ).
 If stimulus is greater, the effect on INa
exceeds that on the IK and then, the inward INa
exceeds the outward IK, leading more
depolarization to a point at which AP takes
 The smallest level of depolarization that can

generate action potential is called threshold

*(In general, TP is about 15 mV above the RP of the
The process to generate action
potential is just like shoot with a
or like spark plug firing an

The key that AP is evoked is that

energy used in depolarization should
be greater enough to bring membrane
potential to the threshold potential.
Once membrane potential is
depolarized to threshold potential,
then the occurrence of an action
potential is inevitable. Because…

A process of positive feedback

 A key to generate action potential is to make
membrane depolarization to the threshold level no
matter what kind of manner.
The peak of the action potential is determined not
by the depolarizing stimulus but rather by the
sodium equilibrium potential ([Na]o/[Na]i)
stimulus and local
Graded (electrotonic) Potential
Now consider subthreshold stimuli
–the membrane potential doesn’t reach the
threshold voltage
–The local currents still flow but slowly the membrane
potential returns to the resting value
If the stimulation is restricted to a small area of
–the depolarization will be greatest at that point and
will fall exponentially with distance
because the effect is ‘local’ to the stimulus,
these are called ‘electrotonic’ or ‘local’
Properties of local response
Importantly, local potentials:
– do not induce refractoriness
–are graded
bigger stimulus = bigger response!
–Summate (spatial or temporal summation)
multiple stimuli = summed response



Voltage response (%)

Recording electrodes


3 6 Distance (mm)
Comparison of the Action
Potential and Local Potential
Action potential Local response
 “All” or “none”  Graded( 等级的)
 Propagation  Electrotonic (电紧
张) propagation
without decrement
 Summation (总和 )
 Refractory  Small amount of Na
 Regenerated Na influx in response to
influx that rely on subthreshold stimulus
Na concentration
out of cell
Propagation of the
action potentials along
nervous or muscle fiber
The role of the action potential,
which is a local event in excitable
cells, is to generate an electrical
signal which is conducted along
the surface of excitable cells as a
command or a message, a piece of
 动作电位是细胞的语言,是细胞携带或传递信息的方式
 细胞以动作电位的频率编码信息量、信息种类等

For example:
In muscle a rapidly conducted action potential ensures that the
whole contractile of mechanism of
a cell is activated at once; In nerves, when the message reached
the terminals, the information is transmitted to adjacent cells by
the release of neurotransmitters.
Mechanism of propagation

 Propagation of action potential

down a unmyelinated ( 无髓鞘的)
nerve or muscle by the spread of
local current from active
regions to adjacent resting
regions in a continuous manner.
Mechanism of propagation
 In myelinated nerves, action
potentials are not generated at
all points along the nerve but
only at gaps in the myelin
(nodes) where the nerve
membrane is not covered. This is
called saltatory (leaping)
conduction ( 跳跃式传导) .
Properties of propagation of
action potential along nerve
 “All” or “none” (“ 全”或“无”)
 Two way directional propagation
 Insulation (绝缘传导)
 Relative fatigueless ( 相对不疲劳)
Review - explain six characteristics
listed at outset in terms of channel
 AP is triggered by depolarization
 because voltage-gated sodium channels
are activated by depolarization
 depolarization must exceed threshold
value to trigger AP
 a depolarization of a certain magnitude is
required to produce significant sodium
 the depolarization must be large enough
for the entering sodium current to exceed
the exiting potassium current
 only then is the positive-feedback cycle
controlling sodium entry set into motion
 AP is all-or-none
 the peak of the action potential is
determined not by the depolarizing
stimulus but rather by
 the sodium equilibrium potential
 the time course of sodium inactivation

 the onset of inactivation prevents the peak of

the action potential from reaching the sodium
equilibrium potential.
 AP propagates without decrement
 because the AP in one region of the membrane causes
the depolarization that triggers an AP in an adjacent
region (unmyelinated axons) or node (myelinated
 AP involves reversal ("overshoot") of membrane
 peak of AP comes close to the sodium equilibrium
potential, which is in the vicinity of +60 mV
 AP is followed by refractory period
 absolute refractory period during which
no stimulus can initiate another AP
 due to sodium inactivation
 followed by relative refractory period
during which another AP can be initiated,
but only by a larger stimulus than required
in the resting state
 recovery from sodium inactivation is not yet complete
(more sodium channels are inactivated than during the
resting state) and
 in membrane regions containing voltage-gated or calcium-
activated potassium channels, potassium conductance is
elevated during the relative refractory period, making it
more difficult to produce an entering sodium current that
exceeds the exiting potassium current (the necessary
condition for triggering a new AP)
Landmark 1952 Papers on Electrical
Activity in the Squid Giant Axon (I)
1. HodgKin AL, Huxley AF, Katz B (1952) Measurement of
current-voltage relations in the membrane of the giant
axon of Loligo. Journal of Physiology 116: 424-448
2. HodgKin AL, Huxley AF (1952) Currents carried by
sodium and potassium ions through the membrane of the
giant axon of Loligo. Journal of Physiology 116: 449-472
3. HodgKin AL, Huxley AF (1952) The components of
membrane conductance in the giant axon of Loligo.
Journal of Physiology 116: 473-496
Landmark 1952 Papers on Electrical
Activity in the Squid Giant Axon (II)
4.HodgKin AL, Huxley AF (1952) The
effect of membrane potential on
conductance in the giant axon of
Journal of Physiology 116: 497-506

5.HodgKin AL, Huxley AF (1952) A

quantitative description of
current and its application to
conduction and excitation in nerve.
Declan A. Doyle, Joa˜ o Morais Cabral, Richard A.
Anling Kuo, Jacqueline M. Gulbis, Steven L.
Brian T. Chait, Roderick MacKinnon*. The
Structure of the Potassium Channel:
Molecular Basis of K1Conduction and
Selectivity. SCIENCE ,VOL, 280, APRIL
Mechanism of initiation
 define and illustrate positive
 positive feedback adds part of the
output of a system to its input

(negative feedback) subtracts part of the
output of a system from its input)
 example of positive feedback: ignition of gas/air mixture
in the engine of your car
 spark from spark plug increases the temperature of nearby
molecules of fuel and oxygen, causing them to react
 the reaction gives off heat
 some of this heat (output) further increases the temperature of
the gas/air mixture (input)
 thus, explosions, exemplify positive feedback
 this drives additional chemical reactions, which give off
additional heat, which promote additional reactions, etc.
 note that this instance of positive
feedback has a well-defined threshold
 if spark is too weak, insufficient heat is given
off (the heat liberated by the chemical
reactions is less that the heat that conducts,
convects and radiates away from the spark
 reaction dies out, and car doesn't start

 relationship between membrane potential

(Em), sodium conductance (gNa ), and
sodium current (INa ) is one of positive
 idea of voltage-gated conductance
 sodium activation: increase in gNa due
to depolarization
 increase in conductance reflects a voltage-
induced change in the shape of the sodium
 displacement of a highly charged region called
the "m gate"
 this displacement acts as if to open a pore, thus
the m gate is said to be opened by depolarization
 Where does the initial depolarization come from?
 at initial segment, stimulus is the summed
depolarizations produces by post-synaptic potentials
 at other segments, stimulus is current sourced by
approaching AP
 in sensory neurons, depolarization is coupled to the
action of a stimulus, such as the stretch of a muscle or
the deformation of the skin
 if depolarization is too small, no action potential is
 why? Exiting potassium current exceeds entering sodium
 recall that depolarization will increase IK
 if increase in INa < increase in IK then Em will return to resting
 at threshold, INa = -IK;
 as soon as INa exceeds IK, positive feedback sets in, and an action
potential is initiated