Excitation–contraction (EC) coupling is the coordination of
two processes that are needed for the generation of force;
the transmission of the nerve stimulus to the triad followed
by the release of calcium from the cisternae of the sarco-
plasmic reticulum and the interaction between actin and
myosin that forms cross-bridges. Many (but not all) of the
molecular events during E–C coupling have been defined.
Briefly, the action potential that arrives to the muscle fiber
membrane is conducted to the interior of the muscle cell
via the transverse tubular (T tubule) system. The nervous
impulse arrives in the triad where the T tubule is in close
proximity with the terminal cisternae of the sarcoplasmic
reticulum that stores calcium. A voltage sensor subunit of
the dihydropiridine receptors on the T tubule opens and
allows an inward current of calcium. This calcium
current triggers the opening of the ryanodine receptors in
the terminal cisternae of the sarcoplasmic reticulum and
releases large amounts of calcium into the sarcoplasm. The
calcium released into the sarcoplasm then binds to the
regulatory protein troponin C on the actin thin myofila-
ment. This initiates a series of molecular events that dis-
place the tropomyosin blocking the active site of the actin
filament.
W. R. Frontera, J. Ochala: Muscle Structure and Function
123
A detailed description and discussion of the events that
follow is beyond the scope of this brief review. Suffice it to
say that the exposure of the active site on actin allows the
binding of the head of the myosin molecule with actin.
ATP and the ATPase located in the myosin head, facilitate
the detachment of myosin from actin (a cross-bridge
formed in a previous contraction) and the formation of a
new cross-bridge. The detailed structure of the myosin
head was described for the first time in 1993 and
contributed significantly to our understanding of the
mechanics and physiology of this process. As mentioned
above, the end-result of this sequence of events is the
sliding of the actin and myosin filaments and the generation
of force. Recent evidence suggests that this sequence of
events within the cell is modulated by several genes
including MTMR14, MG29, and KLF15.