Introductory Physiology

(BBT221)

Lec 14,15: Muscular system

Md. Asaduzzaman Khan, PhD (MAKN)

Dept. of Biochemistry & Microbiology,
North South University
Email: asaduzzaman.khan@northsouth.edu
 Physiology of muscle cells
• Muscle contraction is a cellular phenomenon.
• Universal Characteristics of Muscle:
– excitability - responds to stimuli (e.g., nervous
impulses)
– Conductivity-ability to produce local effect
– contractility - able to shorten in length
– extensibility - stretches when pulled
– elasticity - tends to return to original shape & length
after contraction or extension
Classification of Muscle Tissue
 Skeletal Muscle

• Skeletal muscle may be defined as voluntary striated

muscle that is usually attached to one or more bones.

• Sk Muscle cells = muscle/myofibers

• The Endomysium that surrounds each muscle fiber, the

Perimysium that bundles muscle fibers together into
fascicles, and the Epimysium that encloses the entire
muscle.
Skeletal Muscle
Microscopic anatomy

•Sarcoplasmic reticulum - surround myofibrils

longitudinally
•Ca2+ reservoir
Muscle Fibers
Muscle Fibers
 MYOFIBRILS
Consist of 3 types of myofilaments:
1. Thick filaments – 300 myosin molecules
– two peptide chains with globular heads – form cross bridges b/t thick
and thin filaments
– heads have actin binding sites and ATPase enzymes
2.Thin filaments
– actin strands (2) contain binding sites for myosin heads
– tropomyosin strands block these sites in relaxed muscles
– troponin complex binds to actin, tropomyosin, and calcium
3. Elastic filaments (titin)
– attaches thick filaments to Z disc; holds thick filaments in place;
prevents muscle cell from overstretching
Dystrophin – accessory protein links thick filaments
Striations and Sarcomeres
 Striations and Sarcomeres
❑ A band: Dark band formed by parallel thick filaments that partly overlap
the thin filaments (all three myofilaments)

❑ H band: A lighter region in the middle of an A band that contains thick

filaments only; thin filaments do not reach this far into the A band in
relaxed muscle

❑ M line: A dark line in the middle of an H band; meshwork of proteins

which anchor thick filaments, origin of the thick filaments
❑ I band: A light band composed of thin filaments only, also elastic filaments

❑ Z disc: A protein disc to which thin filaments and elastic filaments are
anchored at each end of a sarcomere; appears as a narrow dark line in
the middle of the I band, anchors thin and elastic filaments
 Motor unit
❑ Axons (fibers) of somatic motor neuron divide as they
enter muscle
❑ Motor unit = one nerve fiber and all muscle fibers
innervated by it
❑each muscle gets at least one motor nerve, wh/ contains
hundreds of motor neurons w/ their axons
❑one axon branches to many terminals, each forms
junction w/ one muscle fiber
❑muscle fibers in a motor unit spread throughout muscle,
not clustered together
❑small vs. large motor units
Motor unit
 Neuromuscular Junction
❑ Each fiber ending forms neuromuscular junction (synapse) w/ a
muscle fiber at motor end plate
❑ synaptic cleft
❑ axonal ending has synaptic vesicles w/ ACh
❑ highly folded sarcolemma of motor end plate has receptors for ACh
(also ion channels)
❑ Nerve impulse reaches end of axon→ voltage-gated Ca2+
channels open → Ca2+ influx causes vesicles to fuse w/axon
membrane → ACh released
❑ ACh binds to receptors on sarcolemma →triggers
depolarizationaction potential
❑ Acetylcholinesterase on sarcolemma breaks down ACh, prevents
continued muscle contraction
 Generation of action potential
1. Recall resting membrane potential:
2. Binding of ACh opens chemically gated ion channels;
Na+ gate opens, Na+ in causes depolarization at motor
end plate (end-plate potential)
3. Voltage-gated channels on sarcolemma next to end
plate open, create action potential that propagates
along memb
4. Immediately Na+ gates close and K+ gates open, K+
rushes out and makes inside neg. again
(repolarization).
 Excitation-contraction coupling
A. Action potential moves down T tubule in triad
B. Terminal cisternae of SR release Ca2+ into sarcoplasm via voltage-
gated channels
C. Ca2+ binds to troponin which shifts tropomyosin
D. Binding sites on actin exposed to myosin heads
E. ATP bound to myosin heads hydrolyzed which activates myosin head
F. Myosin heads attach and pull thin filaments toward center of
sarcomere
G. ATP binding to head releases it, hydrolysis of ATP cocks head for
another stroke, etc.
H. Active transport of Ca2+ back to SR causes restoration of blocking
action by troponin, and muscle cell relaxes
 Sliding filament contraction model
A. thin filaments slide past
thick filaments to overlap to
a greater extent than when
relaxed
B. nerve impulse →myosin
heads attach to actin in thin
filaments → thin filaments
move to center of
sarcomere, repeats w/ ATP
C. Z bands become closer
together, I bands shorten, H
zone disappears, muscle
fiber shortens
•Cross-
Bridge
cycle
Relaxation
 Muscle metabolism
• ATP sources
– 1. phosphorylation by myokinase and creatin phosphate (phosphagen system)
– 2. glycolysis from stored glycogen (anaerobically)
• Partial breakdown of glucose
• Glucose→pyruvate → lactic acid
• 2 ATP per glucose
• Lactate → bloodstream → liver, kidneys,heart
– 3. Aerobic respiration
• Total breakdown of glucose in mitochondria
• 36 ATP per glucose

• Muscle fatigue – causes:

1. consumption of glycogen, ACh
2. Na+/K+ pump slows w/ declining ATP
3. Lactic acid accumulates
4. K+ accumulates in extracellular fluid

• Oxygen debt
1. O2 reserves replacement – myo, hemoglobin
2. Phosphagen system replenishment
3. Oxidation of lactic acid
4. Elevated metabolic rate requirements
During muscle contraction, ATP is split by myosin ATPase to power
cross-bridge stroking. Also, a fresh ATP must bind to myosin to let the
cross bridge detach from actin at the end of a power stroke before
another cycle can begin.
During relaxation, ATP is needed to run the Ca2+ pump that
transports Ca2+ back into the lateral sacs of the sarcoplasmic
reticulum.
The metabolic pathways that supply the ATP needed to accomplish
contraction and relaxation are
a. transfer of a high-energy phosphate from creatine phosphate to
ADP (immediate source);
b. oxidative phosphorylation (the main source when O2 is present),
fueled by glucose derived from muscle glycogen stores or by glucose
and fatty acids delivered by the blood; and
c. glycolysis (the main source when O2 is not present). Pyruvate,
the end product of glycolysis, is converted to lactate when lack of O2
prevents the pyruvate from being further processed by the oxidative
phosphorylation pathway.
 Smooth Muscle
• Each smooth muscle fiber is a spindle-shaped cell with a
diameter ranging from 2 to 10 µm
• Smooth muscle fibers have a single nucleus

• Two types of filaments

– Thick myosin-containing filaments
– Thin actin-containing filaments.
• Does not contain sarcomeres.
• Contains > content of actin than
myosin (ratio of 16:1).
 Smooth Muscle Contraction
• Depends on rise in free intracellular Ca2+.
• Ca2+ binds with calmodulin.
– Ca2+ calmodulin complex joins with and activates myosin
light chain kinase.
– Myosin heads are phosphorylated.
– Myosin heads binds with actin.
• Relaxation occurs when Ca2+
concentration decreases.