NERVE AND MUSCLE

BY
DR. W. A SAKA
• The resting membrane potential is an electrical
potential difference (voltage) that exists across
the plasma membrane of an excitable cell under
resting conditions.

• The RMP exists because of a small buildup of

negative ions in the ICF, and an equal buildup of
positive ions in the ECF.

• In neurons, the resting membrane potential ranges

from -40 to -90 mV, a typical value is -70 mV

2
• The minus sign indicates that the inside of the cell
is negative relative to the outside.

• A cell that exhibits a membrane potential is said

to be polarized.

• Most body cells are polarized; the membrane

potential varies from +5 mV to -100 mV.

• The resting membrane potential arises from three

major factors:
3
1. Unequal distribution of ions in the ECF and cytosol.
• This is a major factor that contributes to the RMP.

• ECF is rich in Na+ and Cl-. In cytosol, however, the

main cation is K+, and the two dominant anions are
phosphates and amino acids in proteins.

• Because the plasma membrane typically has more

K+ leak channels than Na+ leak channels.

• The number of K+ that diffuse out of the cell into the

ECF is greater than the number of Na+ that diffuse
from the ECF into the cell. 4
• As more and more K+ exit, the inside of the
membrane becomes increasingly negative, and
the outside of the membrane becomes
increasingly positive.

2. Inability of most anions to leave the cell.

• Most anions inside the cell are not free to leave

• They cannot follow the K out of the cell because

they are attached to non diffusible molecules
such as ATP and large proteins.

5
3. Electrogenic nature of the Na+–K+ ATPases.
• Membrane permeability to Na+ is very low because
there are only a few sodium leak channels.

• Nevertheless, Na+ do slowly diffuse inward, down

their concentration gradient.

• Left unchecked, such inward leakage of Na+ would

eventually destroy the RMP.

• The small inward Na+ leak and outward K+ leak are

offset by the Na+–K+ ATPases (sodium–potassium
pumps). 6
• These pumps help maintain the resting membrane
potential by pumping out 3 Na+ as fast as it leaks
in and bring in 2 K+.

• However, the K+ eventually leak back out of the

cell as they move down their concentration
gradient.

• This unequal pumping of Na+ and K+ contribute to

the negativity of the resting membrane potential.

7
• Graded Potentials
• A graded potential is a small deviation from the
RMP that makes the membrane either more
polarized (inside more negative) or less polarized
(inside less negative).

• When the response makes the membrane more

polarized, it is termed a hyperpolarizing graded
potential.

• When the response makes the membrane less

polarized, it is termed a depolarizing graded
potential. 8
• A graded potential occurs when a stimulus causes
mechanically-gated or ligand-gated channels to
open or close in an excitable cell’s plasma
membrane.

• They vary in amplitude (size), depending on the

strength of the stimulus.

• They are larger or smaller depending on how

many ligand-gated or mechanically-gated channels
have opened (or closed) and how long each
remains open.

• The opening or closing of these ion channels

alters the flow of specific ions across the
membrane, producing a flow of current that is 9
• Most graded potentials occur in the dendrites and
cell body.

• This mode of travel by which graded potentials die

out as they spread along the membrane is known as
decremental conduction.

• Because they die out within a few millimeters of

their point of origin, graded potentials are useful for
short-distance communication only.

• Graded potentials can become stronger and last

longer by summating with other graded potentials.

• Summation is the process by which graded

potentials add together. 10
• Generation of Action Potentials
• An action potential (AP) or impulse is a sequence
of rapidly occurring events that decrease and
reverse the membrane potential and then
eventually restore it to the resting state.

• An action potential has two main phases: a

depolarizing phase and a repolarizing phase.

• During the depolarizing phase, the negative

membrane potential becomes less negative,
reaches zero, and then becomes positive.
11
• During the repolarizing phase, the membrane
potential is restored to the resting state of -70
mV.

• Following the repolarizing phase, there may be an

after-hyperpolarizing phase, during which the
membrane potential temporarily becomes more
negative than the resting level.

• An action potential occurs in the membrane of the

axon of a neuron when depolarization reaches a
certain level termed the threshold (about 55 mV
in many neurons). 12
• Threshold stimulus (approx 15 mV) causes
increase in permeability of membrane Na resulting
+

in increased Na conductance (gNa).

• An action potential will not occur in response to a

subthreshold stimulus.

• Suprathreshold stimulus will cause formation of

several APs that has the same amplitude (size)
as an AP caused by a threshold stimulus.

• Therefore, once an AP is generated, the

amplitude of an AP is always the same and does
not depend on stimulus intensity
13
• Depolarizing Phase
• Application of an adequate stimulus causes the
membrane of the axon to depolarize to threshold,
voltage-gated Na channels open rapidly.
+

• Both the electrical and the chemical gradients

favor inward movement of Na and the resulting
+

inrush of Na causes the depolarizing phase of the

+

AP.

• The inflow of Na changes the membrane

potential from -55 mV to +30 mV.

• At the peak of the action potential, the inside of

the membrane is 30 mV more positive than the 14
outside.
• As more channels open, Na+ inflow increases, the
membrane depolarizes further, and more Na+
channels open.

• This is an example of a positive feedback

mechanism.

• During the few ten-thousandths of a second that

the voltage-gated Na channel is open, about
20,000 Na+ flow across the membrane and change
the membrane potential considerably.

15
• The Na+–K+ pumps easily bail out about 20,000 Na+
that enter the cell during a single AP and maintain
the low concentration of Na+ inside the cell.

• Repolarizing Phase
• Here, the voltage-gated Na channel is in an
inactivated state.

• It begins with the opening of voltage-gated K+

channels causing its exit.

• The membrane potential increases towards the

negative side. 16
• Inactivation of Na inflow and acceleration of K
+ +

outflow cause the membrane potential to change

from +35 mV to -70 mV.

• After potentials called after depolarisation occurs at

the end of repolarisation which is due to slow K exit .
+

• This phase is followed by after hyperpolarisation

caused by the slow closure of K channels and the
+

potential becomes more negative.

• With the closure of K channels, the membrane

+

potential reaches the resting state.

17
Properties of Action Potential
1. All or none law: an action potential either occurs
completely or it does not occur at all.

• This characteristic of an action potential is known

as the all-or-none principle.

• An action potential is generated in response to a

threshold stimulus but does not form when there
is a subthreshold stimulus.

18
2. Accommodation
• In excitable tissue, the intensity of stimulus that
is applied should be of threshold value and should
be quickly rising.

• If it is slowly rising, it will not give any response,

as the tissue is accommodating that kind of
current

3. Refractory Period
• During the absolute refractory period, even a
very strong stimulus cannot initiate a second
action potential.

• This period coincides with the period of Na +

19
• Inactivated Na+ channels cannot reopen; they first
must return to the resting state.

• In contrast to action potentials, graded potentials do

not exhibit a refractory period.

• The relative refractory period is the period of time

during which a second action potential can be
initiated, but only by a larger than normal stimulus.

• It coincides with the period when the voltage-gated

K+ channels are still open after inactivated Na+
channels have returned to their resting state. 20
4. Strength-duration relationship
• The minimum strength of stimulus that is
required to elicit a response is called rheobase

• The time required to produce this response is

the utilization time

• If the intensity of stimulus is kept twice the

rheobase, the time taken to excite is chronaxie.

• It is defined as the duration at twice the

rheobase strength . 21
• Chronaxie values are useful in determining the
excitability pattern of tissues.

• Greater the chronaxie, lesser the excitability of

the tissue.

22
 Propagation of Action Potential
• To communicate information from one part of the
body to another, APs in a neuron must travel from
where they arise to the axon terminals.

• In contrast to the graded potential, an action

potential is not decremental (it does not die out).

• Instead, an action potential keeps its strength as it

spreads along the membrane.

• This mode of conduction is called propagation, and

it depends on positive feedback. 23
• When sodium ions flow in, they cause voltage-gated
Na channels in adjacent segments of the membrane
to open.

• Thus, the AP travels along the membrane rather like

the activity of that long row of dominoes.

• In actuality, it is not the same AP that propagates

along the entire axon.

• Instead, the AP regenerates over and over at

adjacent regions of membrane from the trigger
zone to the axon terminals. 24
• In a neuron, an AP can propagate in this direction
only—it cannot propagate back toward the cell
body.

• This is because any region of membrane that has

just undergone an AP is temporarily in the
absolute refractory period and cannot generate
another AP.

• Because they can travel along a membrane

without dying out, APs function in communication
over long distances.
25
 Conduction in an Unmyelinated Nerve Fibre
• In an unmyelinated nerve fibre the AP spreads by
self excitation and self propagation.

• AP formed at a point in the membrane, results in

a local spreading to adjacent regions.

• There will be a local circuit formed between the

positive and negative charges on both sides of
the membrane.

• This is called local response 26

• Local response causes electrotonic depolarisaton
of the membrane .

• When depolarisation reaches the threshold level, an

AP is developed.

• The process is repeated at each successive point

along the membrane until the conduction is
completed along the length of the fibre.

• In unmyelinated nerve fibre, conduction is directly

proportional to the square root of diameter of fibre.
27
• The reason is that, in larger size nerve fibre,
there is lesser longitudinal axoplasmic resistance.

 Conduction in Myelinated Nerve Fibre

• In case of myelinated nerve fibres, the current
flow and ionic flow occur at the nodes of Ranvier.

• At the node of Ranvier, there is greater

capacitance and less resistance.

• When one node or Ranvier is excited, the next

node of Ranvier shows local response. 28
• A local current circuit is formed between the
positive and negative charges through the
axoplasm and ECF.

• This causes electrotonic depolarisation of the

next node of Ranvier ahead.

• When depolarisation reaches the threshold level,

an AP is developed at this node of Ranvier,
bypassing the internode.

• This process is repeated at each node of Ranvier.

29
• Thus, impulse in myelinated nerve fibre jumps
from one node of Ranvier to another node.

• This method of conduction is called Saltatory

conduction.

• The velocity of conduction is greater in

myelinated nerve fibres due to this phenomenon.

• Metabolic efficiency in a myelinated nerve is high

because the impulses only need to be conducted
from node to node.
30
• Secondly, at the node of Ranvier, there is a
maximum number of Na+ channels per square
micron metres of area present.

 Synaptic Transmission
• Synapse is a junction between two neurons
where functional continuity is eistablished through
chemical transmission.

• Synapses are formed between an axon and a

dendrite (axodendritic), an axon with a cell body
(axo somatic) and an axon with another axon (axo
axonic). 31
• The neuron that carries the impulse towards the
synapse is called the presynaptic neuron and the
neuron that receives the impulse is called
postsynaptic neurons.

• Between these 2 neurons, there is a synaptic

cleft with 200 Ao wide.

• The presynaptic and postsynaptic regions in the

synaptic cleft show electron dense appearance
which characterises the presence of synaptic
vessicle and receptors respectively.
32
• The vesicles contain the neurotransmitters, which
can be either excitatory or inhibitory.

• There is also presence of a number of

mitochondria in the presynaptic terminal.

• The postsynaptic membrane contains receptors,

specific for the transmitter that is released.

33
 Mechanism of Synaptic Transmission
• When an AP reaches the presynaptic terminal,
there entry of Ca++ from ECF into the terminal.

• This causes the vesicle membrane to fuse with

the presynaptic membrane and release the
contents (exocytosis).

• The released transmitter is attached to the

receptors on the post synaptic membrane and
produces electrical response.

34
• If there is release of excitatory transmitter, an
excitatory postsynaptic potential (EPSP) is
developed or inhibitory postsynaptic potential
(IPSP), if the released transmitter is inhibitory.

• The released transmitter is either inactivated by

the enzymes present in thesynaptic cleft or
taken up (reuptake) by the presynaptic neurons.

35
 TYPES OF MUSCLES
 Skeletal,
 Cardiac and
 Smooth muscles are the types muscle present.

 The 3 types differ from one another, yet, they

exhibit the basic properties and characteristics of
muscles, namely;
 Excitation and
 Contraction.
 SKELETAL MUSCLES
 It is voluntary muscle
 Its attachment to the skeleton enables us to do
voluntary movements.
 Skeletal muscle is covered by connective
tissues called epimysium.
 The muscle contains a number of fascicles
(bundles) which are covered by a connective
tissue perimysium.
 Each fascicle contains a large number of muscle
fibers and is covered by endomysium.
 SKELETAL MUSCLES
 Each muscle fiber can be called a muscle cell and
the membrane lining it is called sarcolema.
 The muscle fiber is a multinucleated cell and the
nuclei are found beneath the sarcolema.
 The sarcoplasm contains cell organelles such as
golgi apparatus, mitochondria, myogloblin,
sarcoplasmic reticulum, enyme, lipids, proteins,
glycogen e.t.c.
 The muscle fiber consists of a number of myofibrils,
which contains the contractile proteins. Each
myofibril is further subdivided into sarcomere
 Sarcomere
 It is the structural and functional unit of the muscle
which extends between 2 adjacent 2 lines.
 A sarcomere includes a complete ‘A’ band (darker
zone) and one half of I’ band (lighter zone) on either
side of A band.
 In resting state, sarcomere width is 2.2 and when
shortens, it is reduced to 1.6 micrometer.
 Decrease in length of sarcomere, I band and H zone
occurs.
 The length of the contractile filaments namely actin
and myosin and width of A band shows no change
during muscle contraction.
 MYOSIN
 This a thick filament present in the A band and
each thick filament contains 500 – 600 myosin.
 The type of myosin present in muscle is myosin II.
 There are 2 heads for myosin molecule, which are
formed by 2 heavy chains and 4 light chains.
 The N terminal of the heavy chain and 4 light
chain form the 2 heads of myosin.
 Each head has a binding site for actin and
another site acts as ATPase.
 MYOSIN
 Myosin molecules arranged symmetrically on
either side of the centre of sarcomere.
 The orientation of myosin molecule in one half of
sarcomere is opposite to the orientation in the
other half of ssarcomere.
 The heads project from the molecules at an
angle to form cross bridges with actin.
 ACTIN
 It is present in the thin filament. Each filament
contains 200 – 300 actin molecules.
 The structure shows that it is made up of
globular proteins arranged in a double helical
fashion.
 Between the actin heads, the groove, the binding
site for myosin is present.
 Situated in the actin are the 2 regulatory proteins
called tropomyosin and troponin.
 TROPOMYOSIN
 It is in thin filamentous form, present between
the 2 chainsof actin.
 It covers the binding of myosin in actin attached
to tropomyosin, at regular intervals, troponin is
present.
 It is has 3 subunits namely:
Troponin C – gives attachment to Ca++.
Troponin T – gives attachment to tropomyosin.
Troponin I – Inhibits the interaction between actin and
myosin.
 SARCOTUBULAR SYSTEM
 From sarcolema, there’s awell developed
sarcotubular system surrounding the myofibrils
and appears as vesicles and tubular. It consists of:

 Transverse tubular system (T system).

 Sarcoplasmic reticulum (Longitudinal tubular system).

 T system is an inward extension of the plasma

membrane whereas sarcoplasmic reticulum
surrounds the myofibrils and at A – I band junction.
 SARCOTUBULAR SYSTEM
 It forms cisternae.

 This terminal cistern contains Ca++ which is

released, when action potential reaches the triad.
 TRIAD
 In the skeleton muscle, at the A – I band junction,
a triad is formed by these sarcotubular structure,
with a contrally placed
T system and
cisternae of sarcoplasmic reticulum being present on
either side of it.
 There are end feet projections from the T
system to the cisternae.
 This enables the action potential from t system
to reach the terminal cisternae.
 CARDIAC MUSCLE
 It is striated like skeletal muscles , but involuntary
in nature.
 The muscle fiber has branches and interdigitate
with each other.
 Each fiber form separate cell, separated from
others by intercalated disc, which occurs at the Z
lines.
 There are gap junctions where cell membranes of
2 adjacent cells join.
 CARDIAC MUSCLE
 These gap junctions form low electrical
resistance bridges for the conduction of action
potential from one cel to another.
 In this way, cardiac impulses spread to the entire
myocardium through this function syncitium.
 There’s sarcoplasmic tubular system, with T
system facing the 2 line, instead of, at the AI
band junction as seen in skeletal muscle.
 Contraction In the Cardiac Muscle
 Contraction of cardiac muscles shows that Ca++
entry into the cell is intial for excitation,
contraction and coupling.
 The Ca++ release from cisternae is not
sufficient to activate Troponin C.
 Hence Ca++ enters from ECF when the cell is
depolarized.
 The Ca++ influx occurs through dihydroxypin___
channels (cardiac cell has 4 types of Ca++
channels) and after entering the T system.
 Contraction In the Cardiac Muscle
 It causes Ca++ release from the terminal
cisternae. This is known as Ca induced Ca
release.
 The Ca++ concentration in the cardiac cell is
maintained by Na+ - Ca++ exchange transport.
 The action potential recorded from myocardium
shows repolarisation marked as overshoot,
caused by opening of voltage gated Na+ channels.
 RELAXATION
 Relaxation of muscledepends on the active
pumpingof Ca++ back into the terminal cisternae.
 The enzyme that is involed in the active
transport is Ca++ - Mg++ ATPase.
 The Ca++ pump the cisternae results in the
removal of Ca++ from troponin C.
 This causes conformational changes in the
troponin molecule, which makes tropomyosin to
be lifted and rest in the groove of the actin.
 RELAXATION
 These changes will cover the binding sites in the
actin. The interaction between the actin and
myosin gets inhibited by troponin P, resulting in
muscle relaxation.

 Rigor Mortis: Absence of ATP causes myosin

remaining attached to actin, as the cross bridge is
not broken.
 It leads to stiffening of the muscle called rigor
mortis, which is observed after death.
 MUSCLE ENERGETICS
 Muscle contraction (shortening) requires energy
and muscle has been called a machine that
coverts chemical energy to mechanical work.
 This energy courses from the hydrostasis of
ATP. The hydrolysis of ATP yields ADP, inorganic
phosphate and energy.
 The energy released is utilized for cross bridge
formation and power stroke mechanism.
 The muscle sarcoplasm contains a high energy
compound called creatine phosphate, which
contains one energy phosphate
 MUSCLE ENERGETICS
 The ADP which is formed by the ATP hydrolysis,
is rephosphorylated into ATP during muscle
contraction. The chemical reaction proceeds as
follows:
 ADP + creatine phosphate creatine + ATP.
 The energy rich compound creatine phosphate is
readily used for the reaction of ATP anaerobically.
 This process of regeneration will lead to muscle
shortening only for a brief period.
 MUSCLE ENERGETICS
 It muscular effort is marked the other
mechanisms of regeneration of ATP will occur.
They are:

 Anaerobic glycolysis.
 Aerobic oxidation of glucose.
 Oxidation of fatty acids.

 The ATP formed is utilized for rephosphorylating

creatin to creatine phosphate which acts as
energy source for muscle contraction.
 MUSCLE ENERGETICS
 Aerobic glycolysis leads to the formation of
pyruvate which enters tricarboxylic acid cycle
(TCA) where in the presence of oxygen, oxidation
occurs, yielding 38 molecules of ATP.
 Anaerobic glycolysis occurs if the muscular work
is severe, the oxygen supplied will not be
sufficient and hence the anaerobic glycolysis
takes place to give lactic acid instead of pyruvate.
 Lactic acid enters the eori cycle to form glycogen
in the liver.
 MUSCLE ENERGETICS
 The breakdown of glycogen releases glucose in
to the blood.
 The oxidation of fatty acids (beta – oxidation)
yields much greater amount of ATP.
 It has been observed that during rest and
moderate muscular activity, oxidation of fatty
acids form the important source of energy.
 However, during marked muscular work, glucose
oxidation becomes significant, as the lipid
oxidation cannot quickly supply energy.
 MUSCLE ENERGETICS
 Oxygen debt: Prolonged muscle shortening leads
to oxygen deficit, as the supply doesn’t match
with the demand. In this situations, anaerobic
glycolysis occurs as said earlier.
 After the muscular work is over, there’s
increased oxygen consumption which is
proportional to the oxygen deficit.
 The increased oxygen consumption noticed after
consumed is utilized for the oxidation of lactic
acid to replenish ATP and creatine phosphate
stores.