Strength – Duration curve ↑ strength of current → ↓ duration of stimulus application

 Time “t”:

 minimal time needed to excite the tissue below which whatever strong the stimulus is ,

there is no response .

 Imp.: used in diathermy (strong current in duration less than “t”) to produce heat without

exciting the tissue .

 Rheobase “R” = Threshold (minimal)stimulus:

 minimal strength needed to excite the tissue below which whatever long the duration is ,

there is no response .

 time needed for rheobase to excite is called Utilisation Time “U.T” .

 Chronaxie “C”:

 minimal time needed by double rheobase to excite the tissue .

 Imp.: measures the excitability (↑ chronaxie → ↓ excitability & vice versa) .

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 Resting Membrane Potential (R.M.P)
 Def.:  Is the potential difference bet. outer & inner surfaces of the membrane .

 All the cells of the body are present in a polarized state (excess +ve charges on outer

surface & excess -ve charges on inner surface) .

 Is the cause of excitability .

 R.M.P of the nerve = - 70 → - 90 mv .

 Record:

If the 2 microelectrodes are put on inner or outer surface of the nerve , no potential

difference will be recorded (isopotential) .

 Causes:

(1)Selective permeability main cause

Extracellular Fluid (E.C.F) Intracellular Fluid (I.C.F)

● Main cations Na+ (142 mEq/L) K+ (140 mEq/L)

Ca2+ Mg2+
K+ (4 mEq/L) Na2+ (10 mEq/L)

● Main anions Cl- (103 mEq/L) Proteins (40 mEq/L)

HCO3- (28 mEq/L) PO43- (70 mEq/L)

Proteins & PO43- Cl- & HCO3-

 Conc. of K+ intracellularly is 35 times its conc. extracellularly & conc. of Na+ extracellularly

is 10 times its conc. intracellularly .

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 Leak channels in the membrane are 100 times more permeable to K+ (as hydrated K+ is

smaller than hydrated Na+) → K+ outflow is more than Na+ inflow .

 By conc. gradient , K+ will move from inside to outside → more +ve charges on outer

surface .

 By conc. gradient , Proteins (-ve charged) want to move from inside to outside , but

membrane is impermeable to proteins → accumulate on inner

surface which will be -ve charged .

 Now , outside is more +ve & inside is more -ve (Polarized state) .

 K+ outflow stops when: K+ outflow by conc. gradient = K+ inflow by electric gradient

 Equilibrium potential for K+ = - 94 mv (by Nernst equation)

 Nernst equation for K+ :

Conc. of K+ inside 140

EK+ = - 61 mV x log = - 61 mv x log
Conc. of K+ outside 4

= - 61 x log 35 = - 61 x log 1.54 = - 94 mV

 Goldman equation : Calculates membrane potential more accurately because it

takes in consideration 3 factors :
1- Polarity of electric charge on each ion e.g Na+ , K+ & Cl- .
2- Concentrations (C) of each ion on the inside (i) & outside (o) of the membrane .
3- Permeability (P) of the membrane to each ion e.g permeability of the membrane to
K+ is 100 times than to Na+ .

E (mV) = - 61 x log (Ck+ i x PK+) + (CNa+ i x PNa+) + (CCl- o x PCl-)

(CK+ o x PK+) + (CNa+ o x PNa+) + (CCl- i x PCl-)

= - 86 mV

(2)Na+ - K+ pump Contributes to R.M.P by - 4mV

 Pumps 3Na+ outside & 2K+ inside (against conc. & electric gradients) .
ATPase
 The carrier protein has ATPase activity (ATP ADP + P + energy) .
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 Monophasic Action Potential
Spike potential

Potential changes which occur in response to minimal (threshold) stimulus

1 Stimulus artifact:

●Small oscillations in CRO .

●Caused by leakage of current from stimulator to recording electrode .

●Indicates exact time of stimulus application .

2 Latent period:

●Time bet. stimulus application & start of response .

●Can be used in calculation of rate of conduction of nerve impulse .

(Distance / Time = 4 cm / 2msec = 20 m / sec)

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3 Ascending limb (Depolarization “DP”):

(a)Partial DP: ●Slow partial DP where membrane potential becomes less than R.M.P .

●Caused by opening of some outer (activation) gates of voltage-gated

Na+ channels → Na+ inflow .

(b)Rapid DP: ●Occurs when membrane potential reaches firing level (-55 mv) which is

reached by a threshold not by a subthreshold stimulus .

●Caused by opening of more outer gates of voltage-gated Na+ channels

(+ve feedback) → more Na+ inflow .

(c)Complete DP: Absence of polarized state & membrane potential = zero .

(d)Reversal of polarity & overshooting: More +ve charges inside & more -ve charges

outside .

4 Descending limb (Repolarization “RP” = Recovery): Return to R.M.P

●At +35 mv: (a)Inner gates start to close → Inactivation of Na+ channels → Na+ inflow

stops .

(b)Opening of inner gates of voltage-gated K+ channels → K+ outflow ↑↑ .

(opening of K+ channels is slower than opening of Na+ channels) .

●After DP (-ve after potential):

*Membrane potential is less than R.M.P during RP .

*reached when RP is 70% completed .

*K+ channels start to close → ↓ K+ outflow → slow RP .

●Hyperpolarization (+ve after potential):

Membrane potential becomes more than R.M.P before reaching R.M.P .

●Na+ - K+ pump: Pumps 3Na+ out & 2K+ in (needs energy) .

Magnitude of Action Potential is 105 to 135 mv

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 Excitability changes during AP
Absolute Refractory Relative Refractory Supernormal Subnormal
Period(ARP) Period(RRP) Phase Phase
Def. Period during which Period during which Period during Period during
whatever strong the strong stimulus which weak which strong
stimulus is, no produces weak stimulus stimulus
response will occur response produces strong produces weak
(prevents continuous response response
harmful activation
of nerve)
Excitability Zero % Above zero & Above 100 % Below 100%
below 100 % (membrane then becomes
potential is near 100%
to firing level)
Coincides Rapid DP & upper Lower 1/3 of RP till After DP After hyper-
with 1/3 of RP start of after DP polarization

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 ALL or NONE law
 As long as other factors affecting excitability remain constant , a threshold (minimal)
stimulus → max. response (a max. AP in nerve & ms fibers and a max.
contraction in ms fibers) .
 ↑ intensity of stimulus above minimal → No further ↑ in response .
 Structures that obey all or none law:
(1)Single nerve fiber & single ms fiber (direct stimulation) .

(2)Cardiac ms .

(3)Motor unit: A.H.C , its axon , its branches & ms fibers supplied by it (indirect stimulation) .

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 Difference bet. Threshold & Subthreshold stimuli
Threshold (Minimal) stimulus
Action Potential = Nerve impulse
Produces Action Potential transmitted as a Local electrotonic potential changes:
nerve impulse
Properties 1- Obeys all or none law
2- Can’t be graded
3- Followed by ARP
4- Can’t be summated
5- Can be propagated
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Subthreshold (Subminimal) stimulus
Local response
(1)Catelectrotonus :
* A state of partial DP at region of
cathode .
* Caused by addition of -ve charges
at outer surface of nerve membrane .
* Membrane potential is less than
R.M.P(associated with ↑ excitability)
* Magnitude of potential changes
varies according to strength of
stimulating current:
 weak current → up to 7 mv DP
 stronger current → from 7 to less
than 15 mv DP (i.e less than
firing level) .
(Local Excitatory State = LES)
(2)Anelectrotonus:
* A state of hyperpolariztion at region
of anode .
* Caused by addition of +ve charges
at outer surface of nerve membrane .
* Membrane potential is more than
R.M.P(associated with ↓ excitability)
1- Doesn’t obey all or none law
2- Can be graded according to
strength of stimulus
3- Not followed by ARP
4- Can be summated & if repeated
→ firing level → Action Potential
5- Can’t be propagated
 Diphasic Action Potential
(1)At first → No potential difference bet. 2 points

(isopotential) .

(2)When impulse reaches point A → DP → -ve in

relation to point B → Upward (initial

deflection) .

(3)When impulse leaves point A → RP (+ve

charged) → 2 points become isoelectric again

→ deflection returns back to baseline .

(4)When impulse reaches point B → DP → -ve in

relation to point A → downward (end

deflection) .

(5)When impulse leaves point B → RP (+ve

charged) → 2 points become isoelectric again

→ deflection returns back to baseline .

Factors affecting excitability of the nerve

 excitability  excitability
(1)↑ permeability to Na+ (1)↓ permeability to Na+
- Veratrine Membrane stabilizers

- ↓ Ca2+ in ECF - Local anaesthesia as cocaine

(2)Hyperkalaemia - ↑ Ca2+ in ECF

(2)Hypokalaemia (3)Hyponatraemia

(4)Tetradotoxin: blocks Na+ channels

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How to block a nerve impulse

1. Severe mechanical pressure 2. Severe cold 3. Severe ischaemia (↓↓ blood supply)
4. Strong Anelectrotonus 5. Local Anaesthesia as cocaine 6. Alcohol
Familial periodic paralysis
 Def.: a rare hereditary disease characterized by severe skeletal ms weakness with attacks

of paralysis . It is more common in ♀ .

 Cause: Hypokalaemia → ↑↑ conc. gradient bet. intra- & extracellular K+ → ↑↑ diffusion

of K+ from inside cell to outside → ↑↑ +ve charges outside → Hyperpolarization

(↑↑ R.M.P and ↓↓ excitability of nerve & ms) .

 ttt: IV K+ .

Accomodation
 Def.: - Adaptation of nerve fiber to stimulation by gradually ↑ current intensity .

- No response occurs during passage of current but only at make & break .

 Cause: (1)Closure of inner (inactivation) gates of Na+ channels → ↓ Na+ inflow .

(2)Slow prolonged opening of K+ channels .

Types of nerve fibers

A (α , β , γ & δ) B C
Diameter 2 - 20 μ 1-5μ Less than 1 μ
Velocity 20 - 120 m / sec 5 - 15 m / sec 2 m / sec
Duration of 0.5 msec 1 msec 2 msec
spike
Sensitivity More to hypoxia & Bet. A & C More to local anaesthesia
pressure as cocaine
Examples Myelinated somatic Myelinated pre- Unmyelinated fibers
afferents & efferents ganglionic autonomic
↑ diameter → ↑ velocity → ↑ magnitude of AP → ↓ duration of spike & ARP → ↓ chronaxie

→ ↑ excitability of the nerve

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 Compound AP of mixed nerve trunk
 Has different peaks .
 Each nerve trunk contains so many fibers having different diameters , thresholds & rates of
conduction .

Conduction
 Def.: an active self - propagating process which needs energy that propagates nerve

impulse over the surface of the nerve as a wave of negativity .

 Types:

(A)According to direction:-

(1)Normal direction (Orthodromic conduction):

●In afferent (sensory) nerve: from receptors to C.N.S .

●In efferent (motor) nerve: from C.N.S to effector organ .

(2)Opposite direction (Antidromic conduction):

e.g Local axon reflex of triple response .

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(B)According to type of nerve fiber:-

(1)In unmyelinated nerve fibers:

 Stimulation by adequate stimulus in middle part of nerve fiber  reversal of polarity
at this part (outside will be -ve in relation to inside )  area of current sink .
 +ve charges behind & in front this area will enter inside nerve fiber through this area
  membrane potential behind & ahead activated part  electrotonic DP  reaches
firing level  AP  propagated till end of nerve fiber .

(2)In myelinated nerve fibers:

 Activated node of Ranvier  reversal of polarity  +ve charges will jump from the
resting node of Ranvier to activated one  electrotonic DP  reaches firing level  AP
(Impulses jump from one node of Ranvier to another in the form of wave of negativity) .
 This is called jumping (saltatory) conduction .
 Myelin sheath acts as electric & ionic insulator .

 50 times more rapid than conduction in

unmyelinated nerve fibers .

 saves energy: Na+-K+ pump occurs only at

nodes of Ranvier .

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