Nerve & muscle
Dr. Osama Abo El Nasr
0125024745
Nerve
Neuron (nerve cell) is the structural unit of nervous system.
Nerve is formed of large numbers of nerve fibers.
Types of nerve fibers
Myelinated nerve fibers
Covered by myelin sheath interrupted at nodes of Ranvier
Somatic afferent, efferent fibers & autonomic preganglionic fibers
Non-myelinated nerve fiber
Not covered by myelin sheath (but surrounded by Schwann cells)
Postganglionic autonomic fibers & other nerve fibers < 1µ in diameter
Characters of nerve fibers: 1- Excitability
2- Conductivity
Excitability :
Stimuli
ability of living tissues to respond to stimuli.
The most excitable tissues in the body are nerves & muscles.
are changes in the environment that excite an organism
Types of stimuli electrical (preferred & used), mechanical, chemical & thermal.
Factors affecting the effectiveness of electric stimulus:
(1) Strength (intensity) of
the stimulus
Certain amplitude can excite
the nerve
(2) Duration of
the stimulus
A certain period can give
response.
(3) Rate of rise stimulus intensity
Rapid  of stimulus intensity:
 gives response.
Slow of stimulus intensity:
 accommodation  no response
The Strength - Duration Curve





The stronger the stimulus, the shorter its duration needed to excite the nerve within limits.
Stimuli of very short duration will not excite the nerve whatever the intensity.
Rheobase (threshold stimulus): The minimal current that excite the nerve.
Utilization time: time needed by rheobase to excite the nerve
Subthreshold (subminimal) stimuli: cause localized
changes in the nerve (local response or local excitatory state)
 Chronaxie: time needed by current twice the rheobase intensity
It is a common measure of excitability.
If excitability of nerve is high, the chronaxie is shortened.
chronaxie of nerve fibers < chronaxie of muscle fibers
Membrane potential
Membrane potential electrical potential (voltage difference) between the inside & outside the cell
(i.e. across the membrane). It is responsible for excitability.
Measuring the membrane potential
CRO to measure very small & very rapid electric changes
Forms of membrane potential
(1) Resting membrane potential: during rest.
(2) Action potential: on stimulation of the nerve by threshold stimulus.
(3) Localized (electrotonic) potentials: on stimulation of the nerve by subthreshold stimulus
(1)
Nerve & muscle
Resting Membrane Potential (R.M.P.)
Dr. Osama Abo El Nasr
0125024745
(polarized state)
Definition electrical potential (voltage difference) between inside & outside membrane surfaces
under resting conditions. The inside is (–ve) : the outside of the membrane
R.M.P.
In large nerve fibers & large skeletal muscles is –90mV.
In medium–sized neurons is –70 mV.
In non excitable cells (RBC’s & epithelial cells) is –20 to –40 mV.
The RMP is (–) means the inside is –ve in relation to outside.
Causes of R.M.P.
(1) Selective permeability of the membrane (for Na + & K+).
(2) Na+ – K+ pump.
(1) Selective permeability of the membrane:
At rest
++++++
Inward rectifying
K+ channels
At equilibrium
140
conc.
electrical
gradient = gradient
+
inside
Na+
conc.
gradient =
K
140
outside
HCO3–
20–100 times
+++++++++++
++
––––––––
+
K
++
proteins –
PO4–3
K+
4
Cl–
Na+
outside
electrical
gradient
14 Na+
inside
(2) Na+ – K+ pump:
Na+- K+ pump is electrogenic
(helps to keep the membrane potential).
Calculation of R.M.P.
1- Nernst equation:
(1) Contribution of K+ diffusion potential
Conc. inside
E (millivolt) = ± 61 × log
Conc. outside
[K+] in
+
EK = – 61 mV × log
[K+] out
140
= – 61 mV × log
= – 61 mV × 1.54 = – 94 mV.
4
(2) Contribution of Na+ diffusion potential
[Na+] in
+
ENa = – 61 mV × log
= – 61 mV × log
+
[Na ] out
14
= – 61 mV × – 1 = 61 mV
140
2- Goldman equation (more accurate)
(CNa+ i x PNa+) + (CK+ i x PK+) + (CCl– o x PCl–)
E (millivolt) = – 61 × log
(CNa+ o x PNa+) + (CK+ o x PK+) + (CCl– i x PCl–)
The calculated R.M.P. by diffusion of ions is – 86 mV. (95% of R.M.P)
Contribution of Na+ – K+ pump: – 4 mV (5 % of R.M.P.)
The net membrane potential of all these factors together at the same time = – 90 mV (the RMP)
Diffusion is the main factor which determines R.M.P. (– 86 mV)
K+ diffusion causes almost all of this R.M.P (due to high permeability of the membrane to it)
(2)
Nerve & muscle
Action potential
Dr. Osama Abo El Nasr
0125024745
Definition Rapid changes in the membrane potential
following stimulation of the nerve by threshold stimulus.
Phases & shape of AP
 Stimulus artifact:
 Latent period: depends on:
 Distance between site of stimulus & recording electrode.
 Velocity of nerve impulse (speed of conduction)
Depolarization phase
Components of AP
Repolarization phase
Hyperpolarization phase
(1) Depolarization phase
Slow depolarization: the 1st 25 mV depolarization
from (– 90 to – 65 mV)
The firing level: (– 65 mV),the level at which the rate
of depolarization increases.
Rapid depolarization: The M.P. rapidly reaches the
isopotential "zero potential" & then overshoots
to (+35 mV) i.e. reversal of polarity
So: the magnitude of A.P. is 125 mV. (90 + 35)
Spike: sharp rise & rapid fall of M.P.(2 mSec)
Hyperpolarization: (35 – 40 mSec)
(2) Repolarization phase
Rapid phase: the 1st 70% of repolarization
Slow phase: the remaining 30% of
repolarization, till the R.M.P. is reached
(3) Hyperpolarization phase
The M.P. overshoots the (R.M.P.) in the
hyperpolarization direction to form small
but prolonged hyperpolarization.
Ionic basis of AP
Determined by:
Voltage gated Na+ channels
Voltage gated K+ channels
Depolarization: (Na+ entry)
Repolarization: (K+ exit)
(1) During depolarization
The initial depolarization:
stimulus  open some of the Na+ channels
 Na+ entry (by electro-conc. gradient)
 The flow of Na+ into the fiber  more
depolarization  more Na+ channels open
& so on (+ve feedback)
Till all Na+ channels are opened (activated).
 At the firing level (– 65 mV)  rapid
depolarization (ascending limb of the spike)
 During overshoot: reversal of M.P.
inactivation of Na+ channels  limits Na+ entry
(2) During repolarization
 Inactivation of Na+ channels  stops Na+ entry
 Activation of K+ channels  K+ exit
(by electro-conc. gradient)
The opening of gates of K+ channels is slower
& more prolonged than opening of Na+
(3) During hyperpolarization
caused by the slow closing of K+ channels
So: K+ conductance (at the end of AP) > during
the resting state  hyperpolarization.
Role of inward rectifier K+ channels: drive membrane potential from hyperpolarization  RMP
(They move K+ inward the nerve only in cases of hyperpolarization)
Re-establishing of Na+ & K+ gradients after AP: (by Na+– K+ pump)
(3)
Nerve & muscle
Dr. Osama Abo El Nasr
0125024745
All or none law
The action potential obeys all or none law
 AP is either generated & conducted maximally or not produced at all
Regardless of the intensity of the stimulus at or above threshold
(provided that other experimental conditions remain constant)
Excitability changes during the AP
 During the initial depolarization up to the firing level, the nerve excitability is increased
 During the remaining part of action potential; the nerve is refractory to restimulation:
(a) Absolute refractory period (ARP)
(b) Relative refractory period (RRP)
It is the period of time during which a second AP It is the period of time during which stronger
cannot occur even with a very strong stimulus. than normal stimuli can produce AP
It extends from the firing level till the end of
It extends from the end of ARP till membrane
the early part of repolarization.
potential returns to its resting state
Cause:
Cause:
The Na+ channels are inactivated: inner gates
(1) Some of Na+ channels return to their resting
are closed & can't be opened for sometime.
state & can be activated
(2) K+ channels are opened widely causing
hyperpolarization
Function of refractory period:
 To protect the nerve from extremely rapid repetitive
stimulation, which would compromise its function
Effect of sub-threshold stimuli
 (Electrotonic potentials)
 (Local response)
 Electrotonic potentials
(a) Catelectrotonus
Occurs at the region of cathode.
A state of partial depolarization (passive)
(< 7mv) due to addition of (–ve) charges by the
cathode at the outer surface of the nerve fiber
The excitability is *; the threshold is 
& M.P. moves closer to the firing level
(b) Anelectrotonus
Occurs at the region of anode.
A state of hyperpolarization due to
addition of (+ve) charges by the anode at
the outer surface of the nerve fiber
The excitability is *; the threshold is 
& M.P. moves away from the firing level
 Local response (local excitatory state)
Action potential
Stimulus: threshold or suprathreshold.
A state of complete depolarization, reversal
of polarity then repolarization
Propagated
Not graded i.e. the magnitude of AP does not
change by changing the intensity of stimulus
Not summated i.e. the magnitude of AP
does not  by addition of another stimuli
Local response
Stimulus: subthreshold.
A state of partial depolarization (below the firing
level) followed by rapid repolarization to RMP
Non-propagated (fades away within 1– 2mm)
Graded i.e. the magnitude of local response 
by increasing the intensity of stimulus
Summated i.e. the magnitude of local response
 by addition of another subthreshold stimuli
 reach the firing level & produce new AP.
Obeys all or none law.
Does not obey all or none law.
Nerve excitability is * up to the firing level, Nerve excitability is * as the M.P. moves
but the remaining part of AP is refractory to
towards the firing level.
restimulation (ARP) & (RRP).
Has no refractory period
N.B. * Excitability changes during nerve stimulation
(4)
Nerve & muscle
Dr. Osama Abo El Nasr
0125024745
Factors affecting excitability of the nerve
 Role of Na+
(1) Factors that  excitability
(2) Factors that  excitability
Conditions that  nerve permeability to Na+ Conditions that  nerve permeability to Na+
 Veratrine.
 Local anesthetics e.g. cocaine
 Low Ca++ conc. in the E.C.F.
 High Ca++ conc. in the E.C.F.
+
  Na in the E.C.F.   AP magnitude but has little effect on R.M.P.
 Block of Na+ channels by tetrodotoxin (TTX)   nerve excitability & no AP could be elicited
 Role of K+
R.M.P. is primarily dependant on conc. gradient of K+ – Repolarization is caused by K+ exit.
(1) Factors that  excitability
(2) Factors that  excitability
 extracellular K+ conc.: makes equilibrium
 extracellular K+ conc.
potential for K+ more –ve  hyperpolarization.
This occurs in a hereditary disease (familial
Makes equilibrium potential for K+ more +ve
periodic paralysis)  marked  nerve
 membrane depolarization
excitability  no nerve impulses produced 
muscle paralysis. It is treated by I.V. K+.
+
Block of K channels by tetraethylammonium (TEA)
 prolonged AP due to prolonged repolarization but hyperpolarization is absent
 Role of Na+ – K+ pump
Re-establishing Na+ & K+ gradients after AP
Block of Na+ – K+ pump affects R.M.P. & genesis of AP
All factors that  the excitability are called membrane stabilizers
Accommodation of nerve fibers
 Gradual “slow”  in intensity of a subthreshold stimulus to threshold level  no response
 It is due to: the slow activation (opening) of Na + channels  slow entry of Na+ is balanced by:
 Inactivation (closure) of Na + channels.
 Opening of K+ channels.
Monophasic & Biphasic AP
Monophasic AP
Recorded if the 2 electrodes are
placed on 1 point of the nerve
(one inside & one outside)
Biphasic AP
Recorded if the 2 electrodes
are placed on 2 points of the
outer surface of the nerve fiber
Compound action potential
 It has many peaks on its descending limb (compound).
Because: the nerve fibers vary in their:
1. Stimulation threshold.
2. Site (distance) from stimulating electrodes.
3. Speed of conduction according to their thickness.

1234-
Compound AP is graded
Subthreshold stimuli  no response.
 stimulus strength to threshold  a small AP
More  the intensity of stimulation   AP amplitude, up to a maximum (maximal stimulation)
More  the intensity of stimulation "Supramaximal stimuli" will not  the amplitude of AP.
(5)
Nerve & muscle
Dr. Osama Abo El Nasr
0125024745
Conduction (propagation) of action potential
 Propagation in unmyelinated nerve fibers:
The stimulated area:  reversal of polarity. The adjacent area:  polarized (resting).
(a) So: potential difference is generated between these 2 areas
& a local circuit of current flow occurs between the depolarized area of the membrane
& the adjacent resting areas.
(b) The adjacent areas become depolarized to threshold  action potential is generated,
while the active segment returns to its resting level.
(c) The new action potential  spreads passively & the process is repeated.
 The speed of propagation α
nerve fiber diameter
 Propagation in myelinated nerve fibers
Saltatory conduction
 The same in principle as in unmyelinated fibers
 The action potentials are generated only at the nodes of Ranvier  AP spreads from one node
to the adjacent one (+ve) charges jump from the resting node to the activated neighboring node
Importance of saltatory conduction:
1-  velocity of conduction of nerve impulse up to 50 folds.
2- Conserves the energy for the axon to be used only at nodes of Ranvier
 The spread of propagation α fiber diameter & internodal distance.
Orthodromic & Antidromic conduction
 Orthodromic conduction: in normal direction (receptors  afferents  terminations)
 Antidromic conduction: in the opposite direction along the nerve fiber
Nerve fiber types
(1) Thickness
(2) Velocity
(3) Spike duration
(4) Susceptibility
(5) Example
A fibers
2 – 20 microns
20 – 120 m/sec
0.5 mSec
More to pressure
& hypoxia.
Myelinated
somatic nerves
Subdivided into: α, β, γ, δ
B Fibers
1 – 5 microns
5 – 15 m/sec
1 mSec
More to hypoxia
& pressure
Myelinated
preganglionic
autonomic nerves
C Fibers
< 1 micron
0.5 – 2 m/sec
2 mSec
More to local
anesthesia
Unmyelinated
postganglionic
autonomic nerves
Metabolism of the nerve
 During rest
Energy is needed to maintain (RMP).
Energy for Na+– K+ pump is derived from
the breakdown of ATP.
Thus, the nerve has a resting heat
while inactive
 During activity
Na pump prevents  Na+ conc. inside the nerve
Na+ pump activity α (Na+ conc. inside the nerve)3
During activity heat production by the nerve is 
It is of 2 types:
ratio
a- Initial heat: (during AP)
1:
b- Recovery heat: (after AP)
30
+
(6)