Download Muscle Tissue

MUSCLE TISSUE:
Structure of myofibril: Low-powered E.M.: Longitudinal units (sacromeres).
(1-2μ m diam.)
Composed of dark A band and lighter I band extending across Z lines. (diagram 1, 2).
High-powered E.M.: A band: thick filaments, I band: thin filaments, interspaced
between thick filaments (diagram 2).
- The Z line bisects the thin filament (I-band) (maintains the thin filaments lengthwise
rigester and hold them together.
- The M line join between thick filaments,
∴ Sacromere extends from one Z line to the next one.
-
Associated with each sacromere:
1- Set of transverse tubules 2- Sacroplasmic reticulum 3- Number of mitichondria.
Muscle Proteins:
1. Myosin: most abundant protein in sk. Muscle (60-70% of total protein), major
protein of thick filaments. Contains: 2 heavy chains (M.W.~ 2x105) – consist of
long (134nm) α-helices wound around each other to form a superhelix, joined to a
double-headed globular region (has ATPase activity & actin binding site). 4 light
chains (two types) (M.W. ~ 2x104): bound to myosin head. They play a role in the
control of contraction by Ca++. (regulatory chains). The essential chains: essential
for ATPase activity (?). Globular region can hydrolyze ATP in absence of light
chains.
2. Actin: Monomeric globular protein (M.W. 42X103): “G” action, 20-25% of total
muscle protein.
“G” actin monomers
Mg2+
elongated polymer (F’ (fibrous) actin)
“up to 103 units”
Actin filament: “2” strings of momomers (F’actin) wound round each other in a
helical form.
minor:
“profilins”: proteins bind to “G” actin, stabilizes the monomer and prevents
polymerization. Also, proteins that cross-link actin strands.
Actin contraction:
musc. cont., cell locomotion, phagocytosis, etc.
3. Tropomyosin: long and thin molecules (M.W. 70 KD): composed of doublestranded
α-helices.
Tropomyasin
molecules
attach
end-to-end
to
form
tropomyosin filament on each actin strand. One tropomyosin filament extends
over 7 actin molecules. Each filament: 1 μm long, containing 300-400 “G” action
molecules and 40-60 tropomyosin molecules. Tropomyosin interacts with actin
and aids in the regulation of the actin-myosin interaction during contraction.
4. Troponin: globular protein (M.W. 76 K.D.), three different subunits:
(1) TpC (M.W. 18KD): Ca2+- binding subunits. 1 structure similar to calmodulin.
Contains “4” divalent ion binding sites. “2” are specific for Ca2+ and the other “2”
are competed for by the Ca2+ and Mg2+. (2) TpI (M.W.24KD): Inhibits the
interaction between actin and myosin. It also prevents activation of myosin
ATPase activity. (3) Tp.T. (M.W. 37 KD): is a tropomyosin-binding subunit. It
binds strongly to tropomyosin as well as Tp-C as a function of Ca2+. It also serves
to anchor Tp-I & Tp-C to the actin-tropomyosin complex. Tp-T and Tp-I but not
Tp-C are phosphorylated by cAMP-dependent protein kinase. In cardiac muscle
(but not sk. muscle), phosporylation of “Tp-I” is accompanied by a decrease in
actin activation of myosin ATPase activity. This may explain the increase in rate
of relaxation of cardiac muscle after epinephrine administration.
Sequence of Events During Muscular Contraction:
1. Electrical impulse from the motor nerve is transmitted to muscle via acetylcholine
release.
2. Electrical impulse is then spread into sacrolemma, which in turn becomes
depolarized.
3. The potential difference disappears as Na+ gets inside cell as K+ leaves the cell.
4. The transverse tubule becomes depolarized and transmits e-impulse to all
myofibrils within muscle fibers.
5. Ca2+ is released from both T-tubule and sarcoplasmic reticulum leading to
increased Ca2+ in sarcoplasm.
6. Ca2+ to troponin-C, which undergoes conformational changes causing the
tropomyosin to move relative to actin exposing myosin binding site (diagram 4),
then actomyosin, ATPase become activated and contraction begins (see below).
Mechanism of Muscle Contraction:
The Cross-Bridge Cycle Model (Huxley):
- The small heads of myosin molecules attach to actin filaments at certain angle.
- It then twists so that the thin filaments are pulled past the thick filaments.
- The heads are then detached. This action pulls the filaments into greater overlap
decreasing the distance between the Z lines and shortening muscle.
Molecular Mechanism (Role of ATP): (Diagram 5):
ATP provides the energy required for muscle contraction. ATP hydrolysis proceeds as
follows:
1. ATP binds to receptor site on the surface of myosin head forming Myosin-ATP
complex.
2. Myosin-ATP complex alters conformation of myosin generating charged MyosinATP intermediate.
3. The charged myosin-ATP intermediate binds very fast to actin molecule in the
thin filament.
4. Soon after binding ATP is hydrolyzed rapidly
energy.
Causes the cross-bridges to twist
5. Another ATP molecule binds to the “rigor complex” causing detachment of the
cross-bridge. When no ATP is available, low energy complex is very stable
leading to rigor mortis.
Formation and Utilization of ATP:
The amount of ATP in muscle is relatively small. Therefore, phosphocreatine is
readily available energy.
ADP + Creatine-
p
CPK
Creatine + ATP
However, NMR studies showed no significant changes in the rate of p
transfer from creatine p
to ADP.
 No significant coupling between CPK reaction and ATP synthesis.
It was suggested: CPK role: may modulate the concentration of ADP which in turn
indirectly controls oxidative phosphorylation.
creatine
Figure:
Utililzation and
resynthesis o
ATP and creatine- p
creatine - p
Actomyosin ATPase
ATP
ADP+ Pi
Myokinase (adenylate kinase)
/2ADP
Glycolysis, TCA
cycle,
f.a. oxidation
In Sk. muscle: Glycogen
glucose
+ Energy
of muscle
contraction
* 50% of ATP for m.
contraction is supplied
by plasma f.f.a.
β-oxidation
Anaerobic
glycolysis
ATP (Lactic acid
is produced)
In prolonged exercise, oxygenation of muscle increases to maximum. ATP is then
produced aerobically by: glycolysis, TCA cycle, f.a. β-oxidation.
In Cardiac Muscle: (long and sustained contraction):
Readily use fuels requiring anaerobic conditions e.g. f.f.as., lactate, K.B
(f.f.as is preferred).
Muscle Lipids:
Variable amounts of fat. Small amounts of cholesterol and larger quantities of
phospholipids. Smooth muscle ahs the largest amount of cholesterol, cardiac muscle
has the next, and striated muscle has the least. Phospholipid: cholesterol high for sk.
muscle and cardiac muscle and low for smooth muscle. Cholesterol may be involved
in spontaneous muscular activity of smooth and cardiac muscle, while phospholipids
may be involved in the greater energy production in cardiac and sk. muscle.
Types of Human Muscle Fibers:
Type I: Small, red, oxidative, myoglobin: present, many mitochondria acid stable
ATPase, alow twitch, sparse, sarcoplasmic reticular system, broad Z band.
Type II: Large, white, glycolytic, myoglobin: absent, few mitochondria, alkali-stable
ATPase, fast twitch, elaborate sarcoplasmic reticular system, narrow Z band.