EXCITABLE TISSUE PHYSIOLOGY - II

Davis Ngarashi
May 2025
 Muscle
Muscle
Physiology
Physiology
Muscle Special
Tissue Cell Shape Striae Nucleus Control structures

Multi-
Skeletal Cylindrical Yes nucleate & Voluntary None
peripheral Rapid

Involuntary
Cardiac Cylindrical Uninucleate Intercalated
Yes Fatigue-
& branched & central discs
resistant

May be
Uninucleate Involuntary
Smooth Fusiform No Slow, wave single-unit
& central
like or multi-unit
Skeletal
Skeletal muscle
muscle
Skeletal
Skeletal muscle
muscle
 a

a = I band (contains only thin filaments)

b = H zone (contains only thick filaments)
Proteins in a Myofibril

Contractile
– Actin
– Myosin

Regulatory
– Troponin
– Tropomyosin

Structural
– Titin
– Dystrophin
– Myomesin
– Nebulin
Thick myofilament: Myosin
Head

Tail Myosin
head has
ATPase
activity

Two heavy chains

Light chains
Actin filaments

Hinges Body
Cross bridges
Myosin filament
Characteristics
Characteristics of
of skeletal
skeletal
muscle
muscle fibers
fibers
Skeletal Muscle
Physiology of Contraction

• How does all this functional

anatomy work?
• 1st – Synaptic transmission at the
neuromuscular junction (NMJ)
• 2nd – Excitation-contraction
coupling
• 3rd – Contraction-relaxation cycle
Motor unit
Refers to one somatic
motor neuron (i.e., αMN)
and all muscle fibers it
innervates
Dispersed throughout the
muscle
Contract and relax in
unison
Several motor units are
called “MOTOR POOL”
 Muscle Fiber Excitation
• Nerve impulse arrives at axon terminal (NMJ)
• Triggers release of Ach by exocytosis
• ACh diffuses across synaptic cleft
• ACh binds to receptors on muscle motor end plate
• Sarcolemma becomes more permeable to Na+
• Na+ triggers release of muscle action potential
• Muscle action potential travels along outside of
sarcolemma and into T-tubules
• Action potential triggers Ca++ release from SR
• Ca++ binds to troponin C on thin filament
• Tropomyosin is pulled aside, revealing binding
sites
• Myosin links to & pulls actin to contract muscle

Muscle Fiber Relaxation

• Acetylcholinesterase decomposes ACh
in synapse
• Action potential (impulse) ends
• SR actively pumps Ca++ back using SERCA
• Tropomyosin moves back to cover
binding sites
• Myosin heads detach
• Muscle fiber returns to its longer resting
length
Skeletal Muscle
Physiology of Contraction – Neuromuscular
Junction
1. Events at the neuromuscular junction (NMJ)
i. Action potential arrives at the pre-synaptic membrane
ii. Depolarization of membrane opens voltage-gated Ca2+ channels
iii. Calcium influxes into the synaptic bulb
iv. Synaptic vesicle binds to membrane proteins and then release Ach
by exocytosis
v. ACh binds to nicotinic Ach receptors
vi. Na+ influx creates an End Plate Potential (EPP)
vii. EPP spreads to edge of the motor end plate and initiates an action
potential in the sarcolemma
Skeletal Muscle
Physiology of Contraction – Excitation-Contraction
Coupling
2. Excitation-Contraction Coupling Process
i. Action potential spreads along sarcolemma and down T-tubules
ii. Depolarization of membrane alters membrane protein which lead
into Ca2+ is being released into the sarcoplasm
iii. Ca2+ binds to troponin C
iv. Initiates a conformational change in the troponin-tropomyosin
complex exposing the binding sites for myosin on actin
v. Myosin binds to actin (electrostatic attraction) hence contraction
Skeletal Muscle
Physiology of Contraction – Contraction-
Relaxation Cycle

3. Contraction-Relaxation Cycle
i. Myosin upon attaching to actin is hydrolyzed (phosphate
coming from the splitting of ATP by Myosin ATPase)
ii. This changes the conformation of myosin causing it to
bend at the neck towards the m-line
iii. ADP is released by the conformational change during the
“power stroke”
iv. ATP binding site is now available for another ATP (along
with magnesium Mg2+)
v. Splitting of ATP to ADP + P by myosin detaches and
returns myosin to its active state
vi. This single event creates a twitch
Excitation-Contraction
Excitation-Contraction
Coupling
Coupling
Sliding Filament Model – Cross-bridge cycle
Sliding Filament Model
Sliding Filament Model
Sliding Filament Model
Sliding Filament Model
 Rigor Mortis

Body Rigor Mortis Time since death

Temperature
Warm Not yet stiff Dead not more than 3
hours
Pathologists can use
Warm Stiffness starting Dead 3 to 8 hours
rigor mortis to estimate in head
time of death Cold Stiff Dead 9 to 36 hours
Cold No longer stiff Dead more than 36
hours
• Same length • Same tension/tone
• Tension increases (more energy used)
(less energy use) • Length changes
• During standing to • During walking and
maintain posture lifting weights
Clinical & General Application
Muscular Dystrophy
• Inherited disorder that
damages and weakens
muscles
• Sarcolemma tears
during contraction
• Results due to the lack
of a protein called
dystrophin
Dystrophin: necessary for
normal muscle function
 Muscle Fatigue
• Depletion of metabolic
reserves (ATP)
• Damage to sarcolemma and SR
• Accumulation of lactic acid
• Decreased NMJ transmission
• Blood flow interruption
• Psychological causes
• Muscle exhaustion and pain
 Muscle Hypertrophy
 Increases diameter
of muscle fibers
 Increases number
of myofibrils
 Increases
mitochondria,
glycogen reserves

Steroid hormones stimulate

muscle growth
• Growth hormone
• Testosterone
 Muscle Tonus
• Tightness of a muscle
(tension in a muscle at
rest)
• Some fibers are always
contracted
• Hypotonia = flaccidity
• Hypertonia = spasticity
Cardiac
Cardiac muscle
muscle
Cardiac
Cardiac muscle
muscle
• Cardiac muscle fibers modified
into pacemaker (SAN)
• Functions as a “functional
syncytium”
• Similar E-C coupling as skeletal
muscle
• Properties:
 Autorhythymicity (myogenic
activity)
 Excitability
 Conductivity
 Contractility
 Refractory period
Atrial repolarization wave
obscured by QRS complex

 P wave
 QRS complex
 T wave
Refractory Periods
Brief period of time in which muscle cells will not
respond to a stimulus

Skeletal
Muscle
Cardiac
Muscle

 This prevents the heart from going into tetany

 Absolute RP occupies the whole period of systole while RRP occupies
the whole period of diastole
Factors affecting myocardial excitability
and conductivity
4. Blood flow:
■ Insufficient bl flow to cardiac ms  excitability &
myocardial metabolism for 3 reasons:
(1) Lack of O2
(2) Excess accumulation of CO2
(3) Lack of sufficient food nutrients
5. Chemical factors (drugs):
■ Digitalis   excitability and conductivity
Factors affecting myocardial contractility

1. Cardiac Innervation:
■ Sympathetic NS   force of contraction

■ Parasympathetic NS (vagus)   atrial force of contraction

Factors affecting myocardial
contractility
2. Oxygen supply:
■ Hypoxia   contractility

3. Calcium & potassium ions concentration in ECF:

■  Ca2+   contractility
■  K+   contractility

4. Physical factors:
■ Warming   contractility
■ Cooling   contractility
Factors affecting myocardial
contractility
5. Hormonal & chemical factors (drugs):

■ Positive inotropics:
(Adrenaline, noradrenaline, alkalosis, digitalis, Ca2+,
caffeine,…)

■ Negative inotropics:
(Acetylcholine, acidosis, ether, chloroform, some
bacterial toxins (e.g. diphtheria toxins), K+, …)
Rhythmicity (automaticity)

The ability of cardiac ms to contract in a regular

constant manner w/out nerve supply

♥ It’s myogenic in origin (i.e. not neurogenic)

♥ Its initiated by the ‘pacemaker’ of the ht, the

SA- node
♥ Has spontaneous (w/out stimulation)
depolarization, up to firing level
Factors affecting myocardial
rhythmicity:
1. Cardiac Innervation:
a. Sympathetic stimuli:

 Tachycardia, by  spontaneous depolarization of

SA- node

How?
■  SA- node membrane permeability to K+  less K+ efflux
■  membrane permeability to Ca2+  more Ca2+ influx

■ As a result, the slope of depolarization , causing  rate

of SA- node firing &  HR
Factors affecting myocardial
rhythmicity:
2. Effect of ion concentrations
in ECF:
a. K ions:
+

■ If  in ECF   rhythmicity
■ If  in ECF   rhythmicity
(? stop heart in diastole)

b. Na+ ions:
■ If  in ECF  initiate rhythmicity, but can’t
maintain it
Factors affecting myocardial
rhythmicity:
3. Physical factors:
a. Warming:   rhythmicity
b. Cooling:   rhythmicity

c. Exercise:   HR as a result of  sympathetic n.

stimulation &  vagal inhibition to
SA- node
d. Endurance-trained athletes: Resting bradycardia
due to high vagal activity
Factors affecting myocardial
rhythmicity:
4. Chemical factors (drugs):
a. Thyroid hormones & catecholamines:
  rhythmicity

b. Ach:
  rhythmicity

c. Hypoxia:
  rhythmicity
Smooth
Smooth muscle
muscle
 Smooth
Smooth muscle
muscle
• Most smooth muscle fibers contract or relax in
response to:
• Action potentials from the autonomic nervous
system
 Pupil constriction due to increased light
energy
• In response to stretching
• Food in digestive tract stretches intestinal
walls initiating peristalsis
• Hormones
 Epinephrine causes relaxation of smooth
muscle in the air-ways and in some blood
vessel walls
• Changes in pH, oxygen and carbon dioxide
levels
 Types
Typesof
ofsmooth
smoothmuscles
muscles

Single-unit smooth muscle Autonomic

neuron

Nucleus

i.Myogenic contractile activity

(self-excitable)
ii.Contract rhythmically as a
unit
iii.Cells electrically linked by
numerous gap junctions Muscle

(functional syncytium)
fiber

iv.Pacemaker activity
v.Found in the walls of gut,
bile ducts, uterus, bladder,
ureters and blood vessels
 Types
Typesof
ofsmooth
smoothmuscles
muscles

Autonomic

Multi-unit smooth muscle

neuron

i.Neurogenic contractile
activity
ii.Act as individual units (non-
syncytial) Muscle
iii.Innervated by a single fiber

nerve
iv.Few gap junctions
v.Found in piloerectors, blood
vessels, ciliary body, iris, large
airways, and intestines
Thick myofilament: Myosin
Head

Tail Myosin head

ATPase activity
(slowest)

Two heavy chains

Light chains
Actin filaments

Hinges Body
Cross bridges
Myosin filament
  NO
 Hydralazine
 Nitrates
 sildenafil

Pi
MLC
Phosphatase

Pi
With Pi Without Pi
Active Passive
(Contracted) (Relaxed)

Regulatory proteins
Myosin light chain (MLC)
 Excitation-contraction
Excitation-contraction coupling
coupling

Contraction
Relaxation
 Latch
Latch mechanism
mechanism
High
High force-
force- Low
Low energy
energy

• It is the state in which

dephosphorylated
myosin head unable
to detach from actin
(similar to “rigor mortis”
in skeletal muscle)
• This results in
sustained contraction
without consuming
too much ATP and
getting fatigue easily
 Comparison
Comparisonof
ofskeletal,
skeletal,cardiac
cardiacand
andsmooth
smoothmuscle
muscle

Characteristic Skeletal muscle Cardiac muscle Smooth muscle

Striations (sarcomere) Yes Yes No
SR Well-developed Moderately developed Poorly developed
T-tubules Yes, aligned with each A-I Yes, aligned with each Z No
band disc
Gap junctions No In the intercalated discs In visceral smooth muscles

Ca++ sources SR SR and interstitial fluid Mostly ISF and few SR

Regulator proteins Troponin and tropomyosin Troponin and Calmodulin and MLCK
tropomyosin
Pacemaker activity No Yes In visceral smooth muscles
Myosin ATPase activity Fastest Intermediate Slowest

Recruitment/proliferation Yes No In visceral smooth muscles

Level of control Voluntary Involuntary Involuntary
Neural input Somatic (Ach) ANS (Ach and NE) ANS (Ach and NE)
Neuroeffector junction NMJ Varicosities Varicosities
Speed of contraction Fast , easily fatigued Moderate, never get Slow, don’t get fatigued
fatigued
Hormonal control None Several Epinephrine
Your attention is highly appreciated!!
Thanks..