Page 313 - Biomedical Engineering and Design Handbook Volume 1, Fundamentals

290 BIOMECHANICS OF THE HUMAN BODY

the synaptic cleft. Acetylcholine diffuses across the synaptic cleft and binds to the nicotinic acetyl-
+
+
choline receptors of a transmitter-gated Na -K channel. When bounded by the acetylcholine, the
+
+
+
+
channel is open, and Na flows into the muscle cell and K flows out. The flow of Na and K gener-
ates a local depolarization of the motor end plate, known as end-plate potential. This depolarization
spreads and further triggers a sarcolemmal action potential from the sarcolemma in the region of the
neuromuscular junction.
Once the action potential from the CNS has been transformed into a sarcolemmal action poten-
tial, several processes are necessary to convert the action potential into a muscle fiber force. These
processes are known as excitation-contraction coupling (Fig. 12.3). (1) The sarcolemmal action
potential is firstly propagated down the transverse (T) tubule. (2) The T-tubule action potential then
triggers the release of Ca 2+ from the terminal cisternae of the sarcoplasmic reticulum into the
surrounding sarcoplasm. (3) When the Ca 2+ concentration in the sarcoplasm reaches a threshold,
2+
Ca binds to the regulatory protein (troponin) embedded along the thin filament. (4) The binding of
2+
Ca then causes conformational change in the troponin, which pulls the attached tropomyosin away
from the myosin-binding site on the neighboring actin. As soon as the myosin-binding site is exposed,
the nearby myosin bonds and interacts with the actin. This interaction of actin and myosin to generate
force is referred to as cross-bridge cycle. The thick and thin filaments slide relative to each other and
exert a force on the cytoskeleton during this cycle. The release of energy by ATP hydrolysis powers
this cycling process. After the action potential ends, Ca 2+ is removed by active transport into the
sarcoplasmic reticulum. The tropomyosin is then restored to block the myosin-binding site, the con-
traction then ends and muscle fiber relaxes.
Sarcolemma

Sarcoplasmic 1
reticulum

Ca 2+ Ca 2+ Transverse
tubule
2

Ca 2+ release and reuptake

Ca 2+
Tropomyosin Troponin
3
Actin

4

Myosin
FIGURE 12.3 The four steps in excitation-contraction coupling (see text for
details). [Adapted and modified from Fitts and Metzger (1993).]