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NERVE MUSCLE PHYSIOLOGY

Properties of nerve fibers
 Excitability: physiochemical change that occurs in a tissue when a stimulus is applied.
 Stimulus: external agent that produces excitability in tissues
When the nerve fiber is stimulated - 2 types of responses occur based on the strength of stimulus:
Action potential or nerve impulse Electronic potential or local response
Develops in a nerve fiber when it is stimulated by a Develops when a stimulus with subliminal strength is
stimulus with adequate strength (threshold stimulus) applied. Action potential does not develop
It is propagated It is non-propagated
Obeys all or none law Does not obey all or none law

Electric properties of excitable tissues (nerve & muscle)

1. Resting membrane potential
2. Local potential
3. Action potential
Differences between electrical potential between nerve & muscle fiber:
Event Nerve fiber Skeletal Muscle fiber
Resting membrane potential - 70mV - 90mV
Firing level - 55mV - 75mV
End of depolarization + 35mV + 55mV

Saltatory conduction
 Rapid conduction of impulses through myelinated nerve fibers.
 Impulse jumps from one node of Ranvier to another.
 Myelin sheath is not permeable to ions, so action potentials are generated only at the unmyelinated nodes of
Ranvier, where there is a high density of Na+ channels.
 This consumes less energy comparatively
 The saltatory length is limited since the longitudinal current grows weaker with increasing distance.
 Before it drops below the threshold level, the signal must therefore be refreshed by a new action potential.

Refractory Period
 It is the period during which the nerve does not give any response to a stimulus.
 Refractory period ends once the membrane potential returns to its resting value.
It is of 2 types:
Absolute refractory period Relative refractory period
Nerve does not show any response at all; even by
Period during which the nerve fiber shows response, if the
extremely strong stimuli since Na+ channels in
strength of stimulus is increased to maximum.
depolarized membranes cannot be activated
Extends from the time when firing level is reached, till
Extends through last 2/3 of time of re-polarization
the time when 1/3 of repolarization is completed
It does not cause fatigability of the nerve fiber Voltage gated K+ channels are open

All or none law: It states that when a nerve fiber is stimulated by a stimulus, it gives maximum response or does not
give response at all.

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There are two types of excitable cells:

 Nerve cells: which transmit & modify impulses within the nervous system
 Muscle cells: which contract either in response to nerve stimuli or autonomously
 An excitable cell reacts to stimuli  by altering its membrane characteristics.

Conduction velocity
 It is higher in myelinated nerve fibers (Unmyelinated nerve fibers have a much greater internal longitudinal resistance
(Ri) & poor insulation. So, the electrotonic transmission of neural impulses  very rapidly. Hence, the conducted impulses
must be continuously “refreshed” by generating new action potentials)
 Increases with the diameter of the nerve fiber (Ri is proportional to the cross-sectional area of the nerve fiber [Ri ∞
1/r2]. Thick fibers require few new APs per unit of length because. Increase in fiber diameter   fiber circumference 
conduction, but the beneficial effect of the smaller Ri predominates)

Resting Membrane Potential (RMP)

 Potential voltage difference across membrane of unstimulated muscle & nerve cells
 RMP is always expressed referring to the inside of the membrane
 During rest, Na-K pump is functioning to stabilize the resting potential
 All living cells have a (resting) membrane potential, but only excitable cells (nerve & muscle cells) can greatly
change the ion conductance of their membrane in response to a stimulus, as in an action potential.

It is due to 4 factors: Neuron - 70mV

1. Active Na/K ATPase pump. Heart - 80mV
2. Passive ion distribution (leakage channels along chemical gradient) Muscle - 90mV
3. K+ diffusion potential (high gK) SA node - 55mV
4. Cl- potential drives Cl- from ICF to ECF.

Action potential
Definition Excitation of a neuron occurs if Em on the axon hillock of a motor neuron or on the MEP changes from
its resting value to a less –ve value (slow depolarization)
Causes of a. Neurotransmitter - induced opening of postsynaptic cation channels
Depolarization b. Electrotonic transmission of stimuli from the surroundings
c. AP follows a pattern typical of the specific cell type, regardless of the magnitude of the stimulus that
generated it.
Ion channels  Voltage gated (VG) channels open in response to change in membrane potential.
 2 types of channels for K+: one always open & one closed in resting cell.
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 Channel for Na+: Always closed in resting cells.

AP is  Increase in Na+ permeability.
produced by  After short delay, increase in K+ permeability
 Stimulus causes depolarization to threshold  opening of VG Na+ channels  electrochemical
gradient inward  gNa+ influx  depolarization  gNa & so on (+ve feedback).

Effective Concentration (mmol/Kg H20) Equilibrium potential

ECF ICF (mV)
K+ 4.5 160 - 95
Na + 144 7 + 80
Ca 2+ 1.3 0.0001 – 0.00001 + 125 to + 310
H+ 4 x 10-5 (pH - 7.4) 10-4 (pH - 7.0) - 24
Cl - 114 7 - 80
HCO 3- 28 10 - 27

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MUSCLE PHYSIOLOGY
Types Voluntary muscles - Skeletal muscle: for locomotion, positional change & convection of
respiratory gases Supplied by somatic nerves
Involuntary muscles Supplied by autonomic nerves
- Cardiac muscle: for pumping the blood
- Smooth muscle: motor of internal organs & blood vessels
Differences Feature Smooth Cardiac Skeletal
Myofibrils Absent Present Present
T tubules Absent Short & broad Long & thin
Depolarization Spontaneous Spontaneous Upon stimulation
Summation Possible Not possible Possible
RMP Unstable Stable Stable
Source of Ca Extracellular SR SR
Neuromuscular junction Not well defined Not well defined Well defined
Control Involuntary Involuntary voluntary
Plain muscle – no cross
Cross striations Well developed Well developed
striations

SKELETAL MUSCLE
Structure  Muscle mass is separated from neighboring tissues by  fascia
 Beneath the fascia, the muscle is covered by  Epimysium
 Muscle fiber bundle or fascicule is covered by  Perimysium
 Each muscle fiber is covered by  Endomysium
 Muscle cell or fibers are  multinucleated with peripheral nuclei located just
beneath the sarcolemma.
 Each striated muscle fiber is invested by a cell membrane  the sarcolemma,
which surrounds the sarcoplasm, several mitochondria (Sarcosome) & myofibrils.

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STRUCTURE OF MYOFIBRIL Each myofibril consists of several two alternating bands:

Light band I band - Isotropic in nature (contain only actin filaments)
Dark band A band - Anisotropic in nature (actin & myosin filaments overlap in
this region)
Isotropic When polarized light is passed thru the muscle fiber, the light rays
are refracted at the same angle
Z lines Are also called the Z plates (Plate-like proteins).
Subdivide each myofibril into striated compartments called
sarcomeres (2μm long).
Sarcomere  The portion of myofibril in between two Z lines
 It is the structural & functional unit of skeletal muscle.
 H zone: lies in the middle of A band. Contains only myosin filaments.
 M line: situated in the middle of H zone. It is formed by myosin binding
proteins.
 Sarcomere consists of myofilaments  action & myosin filaments
 Actin Filaments: Thin filaments, extends to z line, I band & up to H zone of A
band.
 Myosin Filaments: Thick filaments, Situated in A band, including the H zone.
 During contraction: H zone & I band are shortened and the Z lines come closer.
Types of Skeletal Muscle  Contractile proteins: Actin, Myosin
proteins  Regulatory proteins:
1. Skeletal & cardiac muscle – tropomyosin, troponin
2. Smooth muscle - Calmodulin
3. Nebulin: responsible for positioning of action.
4. Titin (Connectin) - connected with Z disc & M disc
 Contractile protein connected with Z disc: Actin
 Contractile protein connected with M disc: Myosin
MYOSIN Types of Myosin
 Myosin I – present in sperms
 Myosin II - present in sarcomere (skeletal muscles)
Structure
- Each myosin filament consists of a bundle of myosin-II molecules.
- Each myosin molecule is made up of 6 polypeptide chains: 2 heavy chains & 4
light chains.
- At one end, the 2 heavy chains twist around each other to form a double helix
– the tail.
- At the other end, both the chains turn away in opposite directions & form –
globular head.
- Each myosin head is attached with 2 light chains (one regulatory & one
essential).
- Each myosin head has 2 sites: an actin binding site & a motor domain with a
nucleotide binding pocket (for ATP or ADP + Pi)
- Conformational changes in the head–neck segment allow the myosin head to
“tilt” when interacting with actin (sliding filaments).
- In the central part of myosin filament (H zone)  Myosin head is absent.

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ACTIN  Each actin molecule is called F actin & it is a polymer of a small protein called
G actin.
 Actin molecules in actin filament are also arranged in the form of a double
helix, which is positioned by the equally long protein nebulin.
 Each F actin molecule has an active site for the attachment of myosin head.
 During rest, Actin is detached from myosin by relaxing (inhibitory) proteins:
 Tropomyosin: covers the myosin binding sites on F-actin molecules.
 Troponin which is formed of 3 subunits:
1. Troponin T: binds to tropomyosin
2. Troponin I: binds with actin & prevents the filaments from sliding when at
rest
3. Troponin C: has two regulatory bindings sites for Ca2+ at the amino end
Other proteins of the muscle  Actinin: Attaches actin filament to Z line.
 Desmin: binds Z line with sarcolemma.
 Nebulin: runs parallel to actin filaments.
 Titin (connectin): Connected to M line (at its carboxyl end) & Z line (at its
amino end). Provides elasticity to the muscle.
 Longest known polypeptide chain & comprises 10% of the total muscle mass.
[When the muscle is stretched, titin unfolds itself. If the stretching is more, it
offers resistance & protects the sarcomere from overstretching.]
 Dystrophin: connects actin filament to to the membrane of muscle cell. It is
connected to sarcoglycans of the sarcolemma.
 Merosin binds the sarcoglycans to the collagen fibrils of the extracellular
matrix.
 Mutation of these proteins leads to muscular dystrophy (Duchenne muscular
dystrophy, limb-girdle dystrophy, congenital muscular dystrophy) implying
the degeneration of muscle fibers with increasing muscular weakness.

Sarco-tubular System
 Formed by: T tubules & L tubules (sarcoplasmic reticulum)
 T tubules: Formed by transverse invaginations of the sarcolemma.
 Function:
o They act as the inward pathway for action potential.
o It contains DHPR which are volt sensitive receptors.
o Sarcoplasmic Reticulum (L tubules)
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o ER is modified as longitudinal tubules with terminal expansion called – cisternae which store Ca ions &
contain RYR1.
 Triad of skeletal muscle: T tubule along with terminal cisternae on either side.
 They are situated at the junction b/w A band & I band.
 When AP reaches DHPR on T tubules, it opens RYR1 on the cisternae  Ca efflux from the cisternae into
sarcoplasm.
 Released Ca binds with troponin C & uncovers the active sites for myosin on actin.

Types of skeletal muscle contraction

Isometric contraction Isotonic contraction
Shortening of central contractile part = lengthening of Shortening of central contractile part as well as shortening
peripheral non-contractile parts & stretching of peripheral ends.
Total length is constant Total tension is constant.
Could be associated with shortening or lengthening
Eg: During upright position in lower sk muscles to
(Lifting or placing down of object with a constant tension
maintain the body posture.
(eg: picking of precious objects very slowly).
No external work done. External work done
In cardiac muscle, this represents isovolumetric contraction; In cardiac muscle, this represents isobaric contraction;
because the muscle length determines the atrial or because the muscle force determines the atrial or
ventricular volume.) ventricular pressure.

 Auxotonic contractions: muscle length & force both vary simultaneously.

 After loaded contraction: An isotonic or auxotonic contraction that builds on an isometric one.

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 Types of skeletal muscle fibers depending on myosin ATPase activity:

o Type I or slow twitch fibers – have small diameter
o Type II or fast twitch fibers – have large diameter. Have two subtypes, FR (2 A) & FF (2 B).
o Each motor unit contains only one type of fiber, this classification also applies to the motor unit.

Based on contraction time, skeletal muscles are classified into two types:
Feature Red (slow) muscles Pale (fast muscles)
Fiber type Type I fibers are more Type II fibers are more
Myoglobin content High, it is red for short term O2 storage Less (FF << FR)
Blood supply Rich Relatively Less
Mitochondria Rich Relatively Less
Sarcoplasmic reticulum Less extensive More extensive
Latent period Long Short
Power of Contraction Less powerful More powerful
Duration of contraction Sustained contraction (longer contraction time) Brief and rapid contractions.
Fatigue Occurs slowly Occurs quickly (FF > FR)
Depends on cellular respiration (aerobic)
Have  conc. of fat droplets (high-energy Depends on glycolysis (anaerobic)
Energy source
substrate reserves) Rich in glycogen (FF > FR)
Rich in oxidative enzymes
Soleus (for upright position), Hand muscles
Examples Back muscles & gastrocnemius
& ocular muscles

Motor End-  It is a type of chemical synapse where transmission of stimuli from a motor axon to a skeletal
plate (MEP) muscle fiber occurs.
 Neurotransmitter  Acetyl Choline
 Receptors at the subsynaptic muscle membrane: NM (Nicotinergic) - Ionotropic cholinoceptors
 The N-cholinoceptor of the MEP (TypeNM) has 5 subunits: (2α, 1β,1γ, 1δ), each containing 4
membrane spanning α-helices.
 Unlike voltage-gated Na+-channels, the open probability po of the NM-cholinoceptor is not
increased by depolarization, but is determined by the Acetyl Choline conc. in the synaptic cleft.
Endplate  It is the change in the RMP (-90mV) when an impulse reaches the NMJ. It is a graded potential.
potential  At RMP, binding of ACh molecule to the two α-subunits  brief opening of channel (specific to
cations such as Na+, K+, Ca2+)  influx of Na+ ions mainly (& a much lower outflow of K+) 
Depolarization of the subsynaptic membrane  endplate potential (EPP)
Miniature end  Release of a small quantity of Ach from the axon terminal  Single-channel currents  that are
plate current summated  yielding miniature end-plate current when spontaneous exocytosis occurs & a
vesicle releases a quantum of ACh activating thousands of NM-cholinoceptors.
 Miniature end plate current: May occur spontaneously due to rupture & release of few Ach into
synaptic cleft due to muscular contraction.
 Can be described as fibrillation – can’t be seen with naked eye.
 If they can be seen with naked eye – they are called twitches.
 But generation of a postsynaptic action potential requires a motor neuron that triggers
exocytosis of 100 vesicles  opening of 200,000 channels at the same time  neurally induced
end-plate current (IEP)

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Termination of synaptic transmission in MEPs occurs by

 Rapid degradation of ACh in the synaptic cleft by acetylcholinesterase localized at the subsynaptic basal
membrane, and
 Diffusion of ACh out of the synaptic cleft

Neuromuscular blockers
 A motor end-plate can be blocked by certain poisons & drugs muscular weakness & paralysis.
 Botulinum neurotoxin: inhibits the discharge of NT’s from the vesicles.
 α-bungarotoxin in snake venom: blocks the opening of ion channels.

Receptor blocker
 Competitive inhibitors to ACh: Curare-like substances such as (+)-tubocurarine  used as muscle relaxants in
surgical operations. Displace ACh from its binding site but do not have a depolarizing effect of their own
MECHANISM OF ACTION OF d-tubercurarine

.
 ACh-like substances: suxamethonium, succinylcholine or carbamylcholine act like Ach & keep the muscle in a
depolarized state.
 Since they are not destroyed by acetylcholinesterase, the muscle remains in a depolarized state for a long time
 paralysis because permanent depolarization also permanently inactivates Na+ channels near the motor end-
plate on the sarcolemma.

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Stimulation of muscle fibers

 Release of Ach at the MEP of sk. muscle  end-plate current that spreads electrotonically  activation of fast
voltage-gated Na+ channels in the sarcolemma  firing of an AP that travels rapidly along the sarcolemma of
the entire muscle fiber & penetrates deep into it thru T tubules
 The extended muscular activity   K+ efflux to ECF  hyperkalemia   muscular resting potential 
inactivation of Na+  temporary muscle paralysis (familial hyperkalemic periodic paralysis)
 Electromechanical coupling
 The conversion of excitation of a muscle into a contraction

In the skeletal muscle:

 This process begins with the AP that excites the voltage- sensitive dihydropyridine receptors (DHPR) of the
sarcolemma in the region of the triads.
 The DHPR are arranged in rows & directly opposite them in the adjacent membrane of the SR are rows of Ca2+
channels called ryanodine receptors (RYR1 in sk. muscle).
 Every other RYR1 is associated with a DHPR.
 RYR1 open when they directly “sense” by mechanical means an AP-related conformational change in the
DHPR.
 In skeletal muscle, DHPR stimulation at a single site is enough to trigger the coordinated opening of an entire
group of RYR1   reliability of impulse transmission.

In the myocardium
 Each DHPR is part of a voltage-gated Ca2+ channel (L-type) of the sarcolemma that opens in response to an
action potential.
 Small quantities of EC Ca2+ enter the cell thru this channel  opening of myocardial RYR2 (trigger effect of
Ca2+ or Ca2+ spark).

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 Ca2+ ions stored in the SR now flow thru the opened RYR1 or RYR2 channels into the cytosol   [Ca2+]i 
saturation of the Ca2+ binding sites on troponin-C  canceling of the troponin-mediated inhibitory effect of
tropomyosin on filament sliding  strong (high affinity) actin-myosin-II binding.

SLIDING FILAMENT MECHANISM OF MUSCLE CONTRACTION

ATP: Essential for filament sliding & hence, for muscle contraction.
Myosin heads act as the motors (motor proteins) of this process  due to their ATPase activity.

Myosin heads connect with actin filaments at an angle forming  cross-bridges.

Conformational change in the region of nucleotide binding site of myosin, (the spatial extent of which is
increased by concerted movement of the neck region)  tilting down of myosin head  power stroke (drawing
the thin filament a length of 4 – 12 nm).

Head then detaches & “tenses” in preparation for the next “oarstroke” when it binds to actin anew.

Kinesin independently advances on the microtubule by incremental movement of its 2 heads, as in tug-of-war.
In this case, 50% of the cycle time is “work time” (duty ratio = 0.5).

Between two consecutive interactions with actin in skeletal muscle, myosin-II “jumps” 36nm (or multiples of
36) to reach the next suitably located actin binding site (C3, jump from a to b).

Meanwhile, the other myosin heads working on this actin filament must make at least another 10 to 100 oar
strokes of around 4–12nm each.

Duty ratio of a myosin head is therefore  0.1 to 0.01.

This division of labor by the myosin heads ensures that a certain percentage of the heads will always be ready to generate rapid
contractions.

When filament sliding occurs:

Z plates approach each other  shortening of I band

Overlap region of thick & thin filaments becomes larger  shortening of H zone

Length of the filaments remains unchanged.

Max. muscle shortening occurs  When the ends of thick filaments bump against the Z plate  overlapping of the
ends of thin filaments.

Shortening of the sarcomere therefore occurs at both ends of the myosin bundle, but in opposite directions.

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Contraction cycle
Binding of ATP to each of the 2 myosin heads (with the aid of Mg2+)  M-ATP complex lying at 45 angle to the
rest of the myosin filament  weak affinity of myosin for actin binding.

Influence of  cytosolic Ca2+ conc. on the troponin–tropomyosin complex  activation of myosin’s ATPase by
actin  hydrolysis of ATP (ATP  ADP + Pi)  formation of A-M-ADP-Pi complex  lifting of myosin heads
(conformational change)  actin-myosin association constant by 104.

1st step of power stroke: Detachment of Pi from the complex  40 tilt of the myosin heads  sliding of actin &
myosin filaments past each other.

2nd step of power stroke: Release of ADP initiates  final positioning of the myosin heads

Remaining A-M complex (rigor complex) is stable & can again be transformed into a much weaker bond when the
myosin heads bind ATP anew (“softening effect” of ATP, D4).
flexibility of muscle at rest is important for: processes such as cardiac filling or the relaxing of the extensor
muscles during rapid bending movement.

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If the cytosolic Ca2+ conc. remains high, the D1 to D4 cycle will begin anew. Depends mainly on whether
subsequent AP’s arrive. Only a portion of the myosin heads that pull actin filaments are “on duty” (low duty ratio)
to ensure the smoothness of contractions.

Ca2+ ions released from the sarcoplasmic reticulum (SR): continuously pumped back to the SR actively by Ca2+-
ATPase (SERCA).

If the RYR-mediated release of Ca2+ from the SR is interrupted, the cytosolic Ca2+ conc. rapidly drops & filament sliding
ceases (resting position).

Parvalbumin:
 It is a protein occurring in the cytosol of fast-twitch muscle fibers (type F).
 Accelerates muscle relaxation after short contractions by binding cytosolic Ca2+ in exchange for Mg2+.
 Its binding affinity for Ca2+ is higher than that of troponin, but lower than that of SR’s Ca2+-ATPase.
 It therefore functions as a “slow” Ca2+ buffer.
o During isotonic contractions (where muscle shortening occurs): The course of the filament sliding
cycle as described above takes place.
o During strictly isometric contractions (tension increases but length remains unchanged): tilting of the
myosin heads & the filament sliding cannot take place.
o Instead, the isometric force is created through the deformation of myosin heads.

Skeletal muscle cramp: no ATP

 For the myosin head to return to its resting state, it needs to be energized.
 Lack of ATP  sk. muscle cramps
 May occur due to ischemia as decreased blood supply  decreased ATP supply.
 If it occurs during death  Rigor mortis

Muscle fibers of a dead body do not produce any ATP. So, after death:
 Ca2+ is no longer pumped back into SR
 ATP reserves needed to break down stable A-M complexes are depleted.
 This results in stiffening of the dead body or rigor (firmness) mortis, which passes only after the actin & myosin
molecules in the muscle fibers decompose.

Sk. Muscle relaxation is active due to two factors:

 Energization of myosin head: binding of ATP to myosin head to bring it back to resting state.
 Active Ca reuptake by longitudinal tubules (by Ca2+ ATPase).

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Treppe or Staircase Phenomenon

 Gradual increase in force of contraction of muscle when it is stimulated repeatedly with a maximal strength at a
low frequency. It is different from summation & tetanus.
 Tetanus: summation of contraction without relaxation due to marked  in the frequency of excitation.
 Tetany:  neuromuscular excitability due to hypocalcemia caused by hypoparathyroidism etc

Tetanus
 It is the sustained maximum contraction of the motor units.
 It occurs if the frequency of stimulation becomes so high that the muscle can no longer relax at all between
stimuli.
 [It occurs at 20 Hz in slow-twitch muscles & at 60–100 Hz in fast-twitch muscles].
 Muscle force during tetanus is as much as 4 times larger than that of single twitches.
 The Ca2+ conc., which decreases to some extent between super positioned stimuli, remains high in tetanus.

Contracture
Not caused by AP’s, but by persistent local depolarization due to:
 [K+] (K+ contracture)
 Drug-induced intracellular Ca2+ release, e.g., in response to caffeine.
Features:
 Contraction of tonus fibers (specific fibers in external eye muscles & in muscle spindles) is also a form of
contracture.
 Tonus fibers do not respond to stimuli acc. to the all-or-none law, but contract in proportion with the
magnitude of depolarization.
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 Magnitude of contraction of tonus fibers regulated by  variation of the cytosolic Ca2+ conc. (not by action
potentials!)
 Individual contractions cannot be detected bcoz because the motor units are alternately (asynchronously)
stimulated.
 [When apparently at rest, muscles such as the postural muscles are in this involuntary state of tension]

Resting muscle tone:

 Continuous & partial contraction of muscles with certain degree of tension. It is maintained by different
mechanisms:
 In skeletal muscle: Regulated by reflexes (reflex tone). It is neurogenic i.e due to the arrival of normal AP’s at
the individual motor units. It increases as the state of attentiveness increases.
 In Smooth & cardiac muscle: It is myogenic i.e muscle themselves control the tone. It depends upon Ca2+ level
& no. of cross bridges.

Muscle extensibility
 A resting muscle containing ATP can be stretched like a rubber band.
 The force required to start the stretching action (extension force at rest) is very small, but increases
exponentially when the muscle is under high elastic strain.

Functional differences between cardiac muscle & skeletal muscle

Skeletal muscle Cardiac muscle
More extensible Less extensible, so the passive extension force at rest is greater.
Operates in the ascending limb (below Lmax) of its length–force curve
Functions in the plateau region of its without a plateau.
length–force curve. So, the ventricle responds to  diastolic filling loads by  its force
development (Frank–Starling mechanism).
Extension also affects troponin’s sensitivity to Ca2+  steeper curve
AP’s are of much longer duration bcoz gK & gCa temporarily after
rapid inactivation of Na+ channels  slow influx of EC Ca2+  plateau
AP’s are of shorter duration.
phase of AP.
Uses IC Ca2+, so no plateau phase.
As a result, the refractory period does not end until a contraction has
almost subsided. So, tetanus cannot be evoked in cardiac muscle.
Have no motor units. The stimulus spreads across all myocardial fibers of
Contains motor units. the atria & ventricles  all-or-none contraction of both atria & thereafter,
both ventricles.
Duration of AP can change the force of contraction (which is controlled by
No change
the variable influx of Ca2+ into the cell).

Frank Starling Law

 Force of contraction is directly proportional to the initial length of muscle fibers within physiological limits.

Energy Supply for Muscle Contraction

 Direct source of chemical energy for muscle contraction  ATP
 A muscle cell contains only a limited amount of ATP– only enough to take a sprinter.
 So, spent ATP is continuously regenerated to keep the [ATP] is constant, even when large quantities of it are
needed.

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 Three routes of ATP regeneration are:

1. De-phosphorylation of creatine phosphate (for short term peak performance)
2. Anaerobic glycolysis (for medium term high performance, occurs in cytoplasm, faster, produces few
molecules of ATP)
3. Aerobic oxidation of glucose & fatty acids (for long term performance, occurs in mitochondria, needs O2,
slower, produces large no. of ATP)
Rigor mortis:
When muscle fibers are completely depleted of ATP and phosphocreatine, they develop a state of extreme rigidity called
rigor. When this occurs after death the condition is called rigor mortis. In rigor almost all of the myosin heads attach to
actin but in an abnormal, fixed and resistant way.

NEUROMUSCULAR JUNCTION: THE MOTOR END PLATE

Sequence of events at NMJ during nerve impulse transmission:

 Nerve impulse (action potential) reaches presynaptic nerve ending
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 As it reaches presynaptic membrane it causes release of acetylcholine into the synapse (synaptic cleft) by a
process of exocytosis
 Acetylcholine, after its release, diffuses within few hundred micro-seconds across the very short distance to the
post synaptic membrane ie, motor end plate
 Acetylcholine attaches to nicotinic A-ch receptors on motor end plate surface and increases the permeability of
motor end plate to Na (mainly) and other positive ions (Eg, Ca2+, NH4+, K+)
 Increased permeability of Na+ (Na+ influx) causes depolarization of the post synaptic membrane causing
generation of local potential, called end plate potential (Non-propagated depolarization).

NERVE IMPULSE TRANSMISSION at NMJ

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Characteristics of Whole Muscle Contraction

1. Isometric contraction - muscle does not shorten
2. Isotonic Contraction - muscle shorten & tension remains constant
Isotonic Contraction
o Muscle shortens against a constant load.
o Work is done to lift the load.
o Eg: Weightlifter lifts a barbell.
Isometric Contraction
o Cross-bridge swinging occurs
o Tension is produced without shortening of the muscle.
o Eg: lifting a load that requires greater tension than can be produced by the muscle.
o No mechanical work is performed.
o Tension is produced, but the muscle does not shorten

Pathological conditions related to NMJ dysfunctions:

Myasthenia Gravis  Auto immune disease
 Antibodies that attack the acetylcholine gated sodium ion transport proteins
 End plate potentials generated is too weak
 Death -paralysis of the respiratory muscles
Muscular Dystrophy  Degenerative muscle diseases.
(MD)  Pseudohypertrophic MD
 X-linked hereditary disease
 Mostly male children
 (1 of 3,500 live male births)
 manifested by progressive muscular weakness
 A characteristic enlargement of the affected muscles, especially the calf muscles
 Gradual degeneration & necrosis of muscle fibers, their replacement by fibrous & fatty
tissue.
 Death usually occurs by the late teens or early twenties
 The most serious defects are in skeletal muscle
 smooth and cardiac muscle are affected as well, and many patients suffer from
cardiomyopathy
Lambert-Eaton LES is caused by auto antibody directed against calcium channels on the motor nerve
syndrome terminals resulting in impaired release of Acetylcholine.

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