Physiology of The Cell: H. Khorrami PH.D

Physiology of the cell
by
H. Khorrami Ph.D.
http://khorrami1962.spaces.live.com
http://www.scribd.com/khorrami4
[email protected]
Muscle types
• Cardiac Muscle
– Striated muscle found only in the heart
– Under involuntary control
– Only rests between contractions
• Smooth Muscle
– Lack striations
– Usually under involuntary control
– Contraction is slow and rhythmic
– Muscles of internal organs
• Skeletal Muscle
– Striated muscle fibers with no clear separation
between cells
– Under voluntary control
Muscles
Neuro-muscular junction
• Synapse
• Motor unit
Synaptic cleft
Synaptic transmission steps
• Na-K conductance
• Depolarization of presynaptic membrane
• Motor end-plate potential
• Increase Ca++ entrance
• Ca2+-calmadulin
• Synapsin-1
• Vesicle fusion
• NT release
Synaptic transmission
Mammalian muscle
(Plasma membrane)
Note alignment
of T-tubules
Myofibril arrangement in muscle
• http://www.youtube.com/watch?v=CepeYFvq
mk4
• https://www.youtube.com/watch?v=hr1M4Sa
F1D4
Titin
• Largest protein with 34,350 AA
• Mutation:
– familial hypertrophic cardiomyopathy
– Tibial muscular dystrophy
T-tubules are NOT
positioned at M lines.
This gap is
actually only
~10 nm.
Ca2+-ATPase
Molecular mechanisms of crossbridge action
This causes a conformational
shift in the myosin head.
Actin filament components and Ca2+ activation
Troponin is a complex of three

proteins including troponin C, a
F
Ca2+-binding protein closely
related to calmodulin.
After death, as ATP runs out,
cytosolic [Ca2+] slowly rises,
actin binding sites are opened,
crossbridges are formed and
become locked in the "rigor"
position without ATP to bind.
Binding of myosin to actin

leads to release of Pi.
Rigor Mortis
Single twitch
Summation of skeletal muscle tension; tetanus
Tetanus
Length-tension curve for skeletal muscle
Full overlap between

thick and thin filaments
Decreasing overlap limits

maximum tension
Actin poking
No overlap
through M line;
(Muscles are not naturally
myosin bumping
stretched to this point)
into Z disk.
Contraction range with

normal skeletal movements
Lmax
Tension in muscle
Elastic elements
• PEE
• SEE
• TEE
Contraction
• Isometric
• Isotonic
– Concentric
– Eccentric
Time is required for maximal twitch force to develop, because some
shortening of sarcomeres must occur to stretch elastic elements of
muscle before force can be transmitted through tendons
By the time this maximal force is developed, [Ca2+] and number of
active crossbridges have greatly decreased, so an individual twitch
reaches much less than the maximum force the muscle can develop
Muscle Metabolism
Mitochondria generate ~32 ATP from one glucose
(slow, but efficient).
Glycolysis generates 2 ATP from one glucose
(fast, but inefficient; lactate accumulates).
Creatine kinase reaction: (fastest)
ADP + creatine-P  ATP + creatine
Adenylate kinase reaction (fast; used when ATP
levels are very low):
ADP + MgADP  AMP + MgATP
Muscle fiber types
Muscle Fatigue
 Central: involving central nervous system
may involve such factors as dehydration, osmolarity, low
blood sugar, and may precede physiological
fatigue of actual muscles
 Peripheral: in or near muscles, accumulation of lactate
and pH, especially in fast-twitch fibers
 inorganic phosphate may increasingly inhibit
cleavage of ATP in the crossbridge cycle or in
the sequestering of Ca2+
Intrafusal Fibers
Muscle Control
Golgi tendon organ
Motor unit
• Small motor unit: 1-to-1 e.g. in EOM
• Large motor unit: 1-to-2000 e.g.
gastrocnemius muscle
Motor Unit: Fibers Innervated from
1 neuron
• "All or none" within
each motor unit
• Fine touch
– 1:1 nerve to fiber
– Finger tips
• Big muscles
– 1: 2000
– Leg muscles
Animation: Muscular System:
PLAY
Contraction of Motor Units
Contractile force
can also be
regulated through
activation of
more, or fewer,
motor units.
Recruitment of Fibers: Produce
Graduated Force
• Weak stimulus
– Lowest threshold fibers
– Slow twitch typically
• Moderate: adds fast
oxidative
• High stimulus: all fibers
• Asynchronous:
– Units take turns
– Prevents fatigue
Hypokalemia, Causes
• Kidney disease
• Diabetes
• Cirrhosis(chronic alcoholism)
• Laxative abuse(loose weight)
• Diuretics
• Steroids,…
– steroid psychosis, mood changes, agitation, and
irrational behavior
• Corticosteroids( organ transplant, Cushing
disease,…)
Hypokalemia,
• Proximal muscle weakness

• Myopathies
• Cardiac arrhythmia
• Hypokalemic periodic quadriparesis
– Autosomal dominant disorder
– Areflexic paresis
– Irregular attacks
– Large carbohydrate meals often precipitate attacks
Hyponatremia
• Compulsive water intake
• Adrenal insufficiency
• Kidney disease
• Hi ADH
• Medications
Hyponatremia
• Osmosis, cell swelling, cerebral edema,..
• Confusion, agitation, stupor
• Nausea and vomiting
• Headache, confusion
• Loss of energy, drowsiness and fatigue
• Restlessness and irritability
• Muscle weakness, spasms or cramps
• Seizures
• Coma
Proprioceptors
• Specialised sensory receptors within joints, muscles,
and tendons
• Sensitive to both tension and pressure
• Play a role in relaying information concerning muscle
dynamics to the conscious and subconscious parts of
the CNS
• They provide the brain with information concerning
kinesthetic sense, or conscious appreciation of the
position of body parts with respect to gravity
• Mostly at subconscious level,
• GTO located in tendons near the myotendinous
junction and are in series
Techniques to Increase ROM
• MET
• PNF( Proprioceptive Neuromuscular
Facilitation)
PNF Theories
• Autogenic inhibition
• Reciprocal inhibition
• Stress relaxation
• Gate control theory
PNF Techniques
• Contract-Relax (CR) method
• Contract-Relax-Antagonist-Contract (CRAC)
Methode
• **PNF before exercise decrease the muscle

performance
• ** PNF after exercise increase the muscle
performance
Ach Agonist
• Stimulate Ach receptor but not destroyed by
AchE:
– Nicotine, carbacol & methacoline
– Produce spasm
Skeletal Muscle Attachment
• Tendon Attachments
– Origin
• Attachment to the bone that doesn’t move
– Insertion
• Attachment to the bone that does move
• Antagonistic Pairs
– Flexor
• Flexes the joint (moves toward the body)
– Extensor
• Extends the joint (away from the body)
Rheobase & chronaxie
Trigger points
• Hyperirritable spots in myofascial tissue
Pathophysiology
• Higher concentration of Ach, NAd, 5HT
• Low PH
Muscle Cramp
• If you’ve ever had a “charley horse” -- that odd
pain in your calf -- you’ve had a cramp. But
they can happen anywhere in your body at
any time, even when you’re asleep. No matter
where you get them, what’s going on inside is
the same: Your muscles suddenly tighten up
when you don’t want them to. Several things
can bring on cramps, but you can do some
things to keep them from happening
Possible Cause: Not Enough Water
• Cramps may be your body’s way of telling you
that you need some, you’re dehydrated
• Other signs include dizziness, headache, and
constipation. So keep water with you and sip it
throughout the day, especially if you’re
outside in hot weather
High Temperatures
• Your body loses fluids when you work or
exercise in the heat, and that can make you
more likely to cramp. This may be partly
because your muscles need water, but it’s also
because you sweat out important minerals
called electrolytes, sodium, potassium, and
calcium
Medications
• Statins, which are used to control cholesterol,
and diuretics, which help your body get rid of
fluid, are just two of the drugs that can bring
on cramping as a side effect
Poor Circulation
• If your cramps get worse when you walk, your
muscles may not be getting enough blood.
That can happen as you get older or if you’re
not very active. It also can be caused by a
condition called claudication, when arteries
are narrower than they should be and blood
can’t get through easily
Monthly Cycle
• Some women get cramps during their periods.
That happens because a woman’s body makes
certain hormones that make the muscles in
her uterus tighten up. This helps push out
blood and tissue, but it can also cause
cramping
Growth
• Kids often get cramps when they go through a
growth spurt. These are sometimes called
“growing pains,” but they may actually be
caused by too much activity, or kids may just
be more sensitive to pain. The cramps happen
most often in the legs and can wake a child
out of a sound sleep. It may help to stretch
the muscle or put a heating pad on the area
for a short time
Exercise
• It’s important to stay active, but if you do too

much all at once or your body’s not used to it,
your muscles can cramp. Instead, pace
yourself: Regular exercise can make your
muscles stronger and harder to tire out, so
they won’t cramp as easily. Be sure to warm
up first, and do plenty of stretching before and
after
How to Feel Better
• Cramps usually go away on their own fairly
quickly, but you can do some things to help
them along. If an activity like running
triggered one, stop right away. Then gently
stretch or massage the muscle or use a
heating pad or hot bath to bring blood to the
area and relax it. Ice and over-the-counter
anti-inflammatories, like ibuprofen, can help if
you have pain and swelling, too
Why Stretching Helps
• Muscles are bunches of fibers that quickly get
smaller or bigger when you move your body
to do something -- from grabbing something
off a shelf to running a race. When you stretch
those fibers regularly, they can do their job
more easily, and that helps you cramp less
Why Your Diet Matters
• Colorful fruits and vegetables have minerals
called electrolytes that help keep your
muscles in good shape and can help you avoid
cramps. Leafy greens and bananas are good
choices
Smooth muscle

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Physiology of the cell

Troponin is a complex of three

Binding of myosin to actin

Full overlap between

Decreasing overlap limits

Contraction range with

• Proximal muscle weakness

• **PNF before exercise decrease the muscle

• It’s important to stay active, but if you do too

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