Download Skeletal Muscle: contractile mechanisms

MCB 32 FALL 2000
SKELETAL MUSCLE: CONTRACTILE MECHANISMS
Reading: Chapter 6, especially pp 156-178.
I. Structure-Function
Cell = fiber. Multinucleate cells because cells fuse during development. Muscle cells in general
do not divide. There can be small amount of repair to damaged muscles from "sattelite cells",
but this is limited. Fig. 6.12
Sarcomere is the functional unit: A bands and I bands. A bands remain constant length during
contraction, while I bands get shorter. Sliding filament model of contraction. Three dimensions
of muscle. Fig. 6.13 and 6.14
Actin (G, globular, and F, filamentous) and myosin (an ATPase, head and tail portions): sliding
filaments. Myosin pulls on actin, which is attached to Z-lines. This leads to contraction.
Strength of contraction generally related to number of interactions between actin filaments and
head groups of myosin. Fig 6.15
Transverse (T) tubules transmit electrical action potential from surface membrane down into the
deeper portions of the muscle.
Contraction initiated by release of Ca from sarcoplasmic reticulum. SR stores and releases Ca.
Storage by Ca pump taking up Ca from the cytosol. Release as described below. Figs 6.15 and
6.20
Actin-myosin cycling with ATP. Fig. 6.20
A.M is rigor state, rigor mortis
+ ATP leads to release of actin from myosin
M.ATP --> M.ADP.Pi.A cocks the head, through ATP being broken down or hydrolyzed. Stores
energy of ATP in cocking of myosin head group. ATPase activity of myosin leads to this change.
At same time, cocked head of myosin binds actin.
M.ADP.Pi.A --> A.M + ADP + Pi. Release of ADP + Pi and movement of myosin head group to
pull on actin and release stored or "cocked" energy of myosin.
Repeat process from beginning.
II. Regulation
Ca, tropomyosin and troponin regulate actin-myosin interaction. Historical aspect.
Tropomyosin is a long molecule lying on top of actin, preventing interaction of actin and myosin.
Troponin bound to tropomyosin, in presence of Ca, pulls on tropomyosin so the molecule is out
of the way and actin and myosin heads can interact. This continues as long as Ca is present.
Excitation-contraction coupling involves the nerve, acetylcholine, action potential. Nerve
releases ACh, which binds to AChR, leading to depolarization of muscle membrane. Once
voltage reaches threshold, action potential is generated in muscle membrane, nearly identical to
that in nerve membrane. Fig. 6.15
AP propogated from muscle-nerve endplate to both ends of muscle, leading to contraction of
muscle. AP is propagated down T tubules, which induce SR membranes to release Ca. This
process is called excitation-contraction coupling. DHP receptor in T tubules change structure
driven by change of membrane voltage (action potential), pull on other proteins ultimately on
ryanodine receptor (RyR), which leads to release of Ca from SR. This continues as AP's are
continually produced in nerve, leading to continual contraction. When action potential stops,
RyR closes, and Ca is pumped back into the SR by the Ca pump, an ATPase which has
similarities to Na/K-ATPase of the plasma membrane.
Thus, contraction is induced by release of stored Ca, which binds to Tn. In turn, Tn pulls
tropomyosin out of the way so actin and myosin can interact and generate tension.
Relaxation occurs because the AP no longer leads to opening of RyR, and Ca ATPase pumps Ca
back into the SR for use in next contraction.
Overall, ATP is used at several levels: ATP is required to maintain Na and K gradients across
the plasma membrane so AP can be generated and conducted. ATP is used to release actin from
myosin, though this does not require hydrolysis of ATP. ATP hydrolysis cocks head of myosin,
storing energy of ATP in movement of head, like cocking spring. ATP is also used to pump Ca
back into the SR following a contraction, leading to relaxation. Fig. 6.20