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Neuron
• Structural unit of the nervous system
• Specialized cell for rapid transfer & integration of information
• Formed of
1. Soma= cell body= processing center
2. Dendrites (↑ surface area): receive signals
3. Axon (nerve fiber)
o Originates from (axon hillock)
o End in many Synaptic Knob: Contain transmitter vesicles or granules
➢ Axon may be short (few mm) if terminate on nearby cell (as in CNS)
Or long (many cm) if terminates on distant cells (skeletal muscle)
Synapse: area of contact between presynaptic and postsynaptic neuron

Types of nerve fibers

A- According to myelination

Myelinated Nerve (thick) Un-Myelinated Nerve (thin)

• Axon is surrounded by myelin sheath, made by • Axon is surrounded by Schwann
Schwann cells without formation of myelin
• Myelin: insulator→ ↓ion flow through membrane
Interrupted by
• Nodes of Ranvier: non-insulated area → ions can
move across the membrane with little resistance
• A & B fiber • C

B- According to thickness & velocity & sensitivity to environmental factors

A (α, β, γ, δ) B C
Diameter 2-20 micron 1-5 micron (µ) < 1 micron
Velocity= rate of conduction 20-120 m/sec 5-15 m/sec 0.5- 2 m/sec
Duration spike 0.5 msec 1 msec 2 msec
Example Somatic motor Preganglionic autonomic Postganglionic autonomic
Blocked by Pressure Hypoxia Anesthesia
Affect C fibers before A
B fibers are most susceptible to hypoxia, C fibers least affected

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Role (contribution) of Ion fluxes & Na+-K+ Pump to resting membrane potential (RMP)

1. Role of the selective permeability for K+, Na+

A-Nernst equation: calculate equilibrium potential for any ion at normal body temperature
concentration inside
• E (millivolt) = ± 61 x log concentration outside

• the sign is positive when the ion is negative (vice versa)

If K+ is the only ion diffuse via the cell If Na+ is the only ion diffuse via the cell
membrane (only factor causing RMP) membrane
RMP = equilibrium potential for K+ RMP = equilibrium potential for Na+
140 1
EK + = -61 mV. X log = -94 mv 𝐄𝐍a+ = - 61 mV. x Log = + 61 mv
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B. Goldman Equation: calculates RMP more accurate by involving

• Concentration of Na+, K+ , Cl- inside and outside.
• Relative Permeability of the membrane to each ions
[𝐶𝑁𝑎+𝑖 X PNa ] + [𝐶𝐾 + i X P𝑘 ] + [𝐶Cl − o X PCl − ]
𝐸 = −61𝑋𝐿𝑜𝑔 + +
[𝐶𝑁𝑎 + o X PNa ] + [𝐶𝐾 𝑜 𝑋 P𝑘 ] + [ CCl − i X PCl − ]

R.M.P. caused by diffusion of ion = - 86 mV. [95 % of R.M.P.]

o Near to K equilibrium potential
o therefore, change in K conc. →leads to marked & serious effects on nerves & muscles)

2. Role of Na+-K+ Pump to R.M.P

• Electrogenic pump
• Causes = -4 mv of RMP

At equilibrium potential:
• Flow of ion in one direction is balanced by its flow in opposite direction
• Equal rate of ion influxes and effluxes

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 Resting membrane potential (RMP)=polarized state

Definition Potential difference between inside (negative) and outside of the membrane at rest
in large nerve & large skeletal muscle fibers -90 mv
In medium sized neurons -70
in less-excitable cells (RBCs, epithelial cells) -20→ -40

Recording 2 microelectrodes (one inside and other outside fiber) connected to voltmeter
(cathode ray oscilloscope)
Causes of RMP u==unequal distribution of ions, caused by
A- Selective permeability of membrane (diffusion): main factor
Concentration difference Intracellular K+ concentration > outside (140/4) = (35/1)
Intracellular Na+ concentration < outside (14/140) = (1/10)
Each ion tries to reach equilibrium potential
Permeability Resting membrane is permeable to K+ (100 times) > Na+
(K+ outflow > Na+ inflow) via leakage- (non-gated) channels ???
Resting membrane is impermeable to intracellular anions (protein)
Net effect inside become negative to outside = potential difference is generated
Causes = -86mv (93%)

B- Na+-K+ Pump
1. Electrogenic pump
Pump 3 Na+ ions out & 2 K+ ions in against concentration gradient (3:2)
2. Result: more +ve ions outside
3. Causes = -4 mv (7%)

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 Action Potential

Definition rapid change in potential following stimulation by threshold (adequate) stimulus

Recording as before
Shape, phases of Action Potential (diagram):
A. Latent period Isoelectric interval between application of stimulus & start of action potential)
• Time taken impulse to travel from stimulating to recording electrode.
• Duration depends on distance between 2 electrodes & speed of conduction in nerve fiber
distance between stimulating & recording electrodes
• Velocity of conduction= latent period

B. Action potential = 3 phases

1. Depolarization (Ascending Limb)

Slow phase -90 to -65 mv= firing level (first 25 mv depolarization)
Rapid phase -65 to zero (iso-potential) then overshoot to +35mv (reversal of polarity)
Amplitude of action potential = 90+35= 125 mv
2. Repolarization (Descending limb)
Rapid phase first 70%
Slow phase 30%
At the end, RMP is reached
3. Hyperpolarization
Potential overshoot in opposite direction →form slight, prolonged hyperpolarization
Then RMP is reached gradually

Duration of action potential

Spike (shar rise & fall) Hyperpolarization
2ms 35-40 ms

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 Ionic basis of action potential

➢ Depolarization caused by Na+ inflow, Repolarization caused by K+ outflow through

Voltage gated Na+ channel (2 gates) Voltage gated K+ channel
outer activation gate inner inactivation gate Only one inner activation gate
closed at RMP opened at RMP closed at RMP
➢ With stimulation, the gates move in sequence
1. Depolarization (positive feedback) (regenerative process) (Na+ inflow)
A. Slow phase (-90 to -65 mv)
• Stimulus → cause initial depolarization (↓ membrane potential from -90 mv to firing level)
→ open Some activation gates of Na + channels
→ Na+ inflow (electrochemical gradient)
→ cause further depolarization
→ more gates open →Until reaching -65mv (firing level or threshold)
B. Rapid phase (-65 to +35mv)
• Opening of all Na channels → cause rush of Na+ in
• Then, rapid inactivation of Na+ channels starts.
(remain inactive for few msec. before returning to resting state)
3. Repolarization
• Cause:
➢ Inactivation of Na+ channels→ stop Na influx & terminate depolarization
➢ Activation of K+ channels → cause K outflow
▪ Slower and more prolonged opening than Na channel (open shortly after Na ch.)
➢ Recovery of Na+ channels: inactivated Na+ must return to resting state ?
4. Hyperpolarization
• Cause: slow closure of K+ channels→ higher K conductance than at rest.
• Leakage K+ Channel:
➢ Non gated, voltage sensitive channels
➢ Drive K+ ions inward only in hyperpolarization,
➢ Drive the membrane potential to the resting state
Re-establishment Na & K gradient after action potential by Na+-K+ pump ??
Action potential will not occur until depolarization reaches firing level
A.P. obeys All or None Rule: (once produced→ propagate with the same amplitude, Duration, shape)
regardless stimulus strength at or above threshold (suprathreshold)
As long as the experimental conditions are kept constant

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 Excitability Changes during the Action Potential

• From initial depolarization to firing level: excitability ↑

• Remaining of A.P.: 2 refractory periods→
➢ ensures one-way forward propagation of AP.
➢ protect the nerve from rapid repetitive stimulation
Absolute refractory period (A.R.P.) Relative refractory period (R.R.P)
excitability = zero excitability below normal
Period during which Period during which
Another action potential cannot be produced Another action potential can be produced by a
whatever stimulus strength stronger stimulus above threshold
From firing level to early repolarization From end of Absolute refractory period
till end of action potential (rest)
Na channels are opened then rapidly Some Na channels return to resting state (active)
inactivated by closure of the Inner gate K channels are opened during repolarization
(K out opposes Na in)

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 Factors affecting Nerve Excitability

1. Role of Na+:

↑ Na+ permeability→ ↓ Na+ permeability (slowly depolarized)

↑ excitability (rapidly depolarized) ↓ excitability (membrane stabilizers)
• Veratridine • Local anesthetics: cocaine
• ↓ Extracellular Ca+2 concentration • ↑extracellular Ca+2 concentration
(hypocalcemia) (hypercalcemia)
Blockade of Na+ channels by tetrodotoxin [TTX] →↓nerve excitability, and no A.P.

ECF Na+ conc. [hyponatremia]→ ↓size of A.P. but has little effect on R.M.P.

2. Role of K+ (RMP is primarily dependent on concentration gradient for K)

↑ ECF K+ concentration (hyperkalemia) ↓ ECF K+ (hypokalemia)
→Make RMP to depolarize→↑excitability → Make RMP to hyperpolarize→↓excitability

Familial periodic paralysis: hereditary hypokalemia

→ ↓excitability
→no nerve impulses
→ Paralysis.
(treated by intravenous K+)

3. Role of Na+ – K+ pump:

• Only prolonged blockage of Na+ K+ pump →affect R.M.P. and genesis of A.P

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 Conduction (propagation) of action potential

A- Conduction in Unmyelinated nerve (continuous conduction) (spread passively)

• A.P. generated at on location acts as a stimulus for generation of new A.P. on adjacent area
1. During reversal of polarity→ potential difference between stimulated depolarized
& adjacent resting polarized areas
2. +ve charge flow passively to –ve area on both outer & inner surfaces →local circuit of current flow.
3. Adjacent area becomes depolarized to firing level →produce action potential,
while active area →return to resting level

B- Conduction in Myelinated nerve (saltatory conduction) (not continuous)

• Same as unmyelinated, however, the cell membrane is exposed to ECF only at node of
Ranvier with numerous voltage gated Na channels
1. A.P. generated only at node, acts as a stimulus for generation of new A.P. on adjacent node
2. +ve charge jump from node to node (saltatory conduction).
3. ↑ diameter of the nerve fiber →↑intermodal distance →↑ speed of propagation
(directly proportional)
• Importance of saltatory:
✓ ↑velocity of conduction (50 fold).
✓ Conserves energy Because only nodes depolarize →little energy (ATP)
for reestablishing Na+ and K+ gradient by Na+ K+ pump

Once the nerve fiber is stimulated, Action potential (impulse) travel in both directions.
Action potential magnitude does not change
Velocity of conduction ↑by:
1) square root of the fiber diameter
2) Myelination
Arrival of action potential to synaptic knob cause release of chemical transmitter

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Orthodromic and antidromic conduction

When Action potential is initiated in the middle →travel in both directions.

In living animal, travels in one direction, i.e. from synaptic junction or receptor
along axon to termination (orthodromic conduction).
Conduction in the opposite direction = antidromic conduction
Synapse (unlike axon), permits conduction in one direction only
Any antidromic impulse fail to pass the first synapse and die out at this point

Local Response [Local Excitatory State]

Definition local partial depolarization due to subthreshold stimuli

Mechanism Subthreshold stimulus →open few Na channels→ slight depolarization
(not enough to reach firing level) followed by rapid repolarization to resting level
Local response differs from A.P. in
A. None propagated (magnitude is insufficient to generate another local response nearby,
and it fades away within 1-2 msec.)
B. Not obey all or none rule
C. No refractory period
D. Graded (magnitude, duration vary with size, strength of stimulus)
E. Summated by rapid repeated subthreshold stimuli to reach firing level &generate action potential.
F. During local response, nerve excitability is ↑, as potential moves towards firing level.

Types of membrane potential

Under resting conditions: RMP

On stimulation
By threshold (adequate) stimuli By subthreshold (inadequate) stimuli
action potential local response

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Accommodation of Nerve Fiber

Definition Gradual “slow” increase in intensity of subthreshold stimulus to threshold level

→ produce no response
Causes slow activation (opening) of Na+ channels →slow entry of Na+ , balanced by
a) Inactivation (closure) of Na+ channels.
b) Opening of K+ channels.

Excitability

Definition: ability of living cells to respond to stimulus (change in environment ).

Membrane potential is the basis of excitability

• Stimuli: change or event which excite an organism → result in response
• Most excitable tissues: nerve and muscle
• Types of stimuli (electrical, mechanical, chemical, thermal)
• Electrical stimulus is preferred because
✓ Similar to natural stimuli inside the body
chronaxie
✓ Controlled
✓ Measured
✓ Not cause tissue damage

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 Strength duration curve

Definition inverse relation between strength of stimuli & duration needed to produce an active response
Factors affecting effectiveness of stimulus
1. Strength (intensity): 2. Duration
• Threshold stimuli (Rheobase): Minimal • Utilization time: Time needed by rheobase to
• intensity needed to excite the nerve → A.P. excite the nerve (response)
• Sub-threshold stimuli→ produce • Chronaxie: Time needed by stimulus double
• local response. rheobase to excite nerve.
• (index of nerve excitability)
If excitability is high, chronaxie is shortened.

✓ Within limits: stronger the stimulus→ shorter the duration needed to excite the nerve
✓ Stimuli of extremely short duration whatever its strength→ produce no response

3. Rate of rise of stimulus intensity:

• Rapidly increased stimulus intensity to threshold → produce response.
• Slowly increased → produce no response [nerve accommodation].

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Monophasic and Biphasic Action Potential

Monophasic action potential inserting one electrode inside & the other indifferent electrode outside
Biphasic Action Potential 2 recording electrodes outside → following changes are observed
At rest No (zero) potential difference between 2 electrodes

When impulse (wave of 1st electrode is negative relative to 2nd

depolarization) reach 1st electrode → wave is recorded
(near to the stimulator) →

When impulse reaches area zero potential difference

between 2 electrodes
When impulse reaches 2nd electrode 1st electrode is positive relative to 2nd
→ wave is recorded in opposite direction.
When impulse leaves 2nd electrode No potential difference

N.B. Can be monophasic by crushing or destroying the nerve between 2 electrodes

or region under 2nd electrode.

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Action Potential in Nerve Trunk "Compound Action Potential"

Definition Action potential recorded from nerve trunks or peripheral nerves (many nerve fibers).
Characters
1. Has Many peaks: as each fiber in the nerve vary in:
a. Threshold
b. Distance from stimulating electrodes.
c. Speed of conduction according to thickness.
activity in fast-conducting fibers arrives at recording electrodes
sooner than activity in slower fibers.
2. graded
A- Subthreshold stimuli None of fibers are stimulated
→no response
B- ↑ intensity to threshold Response of nerve fibers of low threshold
→produce small action potential
C- Further ↑in intensity Action potential ↑ in amplitude, up to maximum.
(maximal stimulation).
D- Supramaximal stimuli No further increase in the amplitude

Neurtrophins

• Certain proteins
• Secreted by glial cells, muscles, or other structures that the neurons innervate
• They are internalized and then transported by retrograde transport to neuronal cell body
• Necessary for neuronal development, growth, survival

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