Ganong's Review of Medical Physiology, 23rd Edition

100
SECTION II
Physiology of Nerve & Muscle Cells

allow for formation of myosin/actin cross-bridges. Upon for-
mation of the cross-bridge, ADP is released, causing a confor-
mational change in the myosin head that moves the thin
filament relative to the thick filament, comprising the cross-
bridge “power stroke.” ATP quickly binds to the free site on the
myosin, which leads to a detachment of the myosin head from
the thin filament. ATP is hydrolyzed and inorganic phosphate
(P
i
) released, causing a “re-cocking” of the myosin head and
completing the cycle. As long as Ca
2+
remains elevated and suf-
ficient ATP is available, this cycle repeats. Many myosin heads
cycle at or near the same time, and they cycle repeatedly, pro-
ducing gross muscle contraction. Each power stroke shortens
the sarcomere about 10 nm. Each thick filament has about 500
myosin heads, and each head cycles about five times per second
during a rapid contraction.
The process by which depolarization of the muscle fiber
initiates contraction is called
excitation–contraction cou-
pling.
The action potential is transmitted to all the fibrils in
the fiber via the T system (Figure 5–7). It triggers the release
of Ca
2+
from the terminal cisterns, the lateral sacs of the sar-
coplasmic reticulum next to the T system. Depolarization of
the T tubule membrane activates the sarcoplasmic reticulum
via
dihydropyridine receptors (DHPR),
named for the drug
dihydropyridine, which blocks them (Figure 5–8). DHPR are
voltage-gated Ca
2+
channels in the T tubule membrane. In
cardiac muscle, influx of Ca
2+
via these channels triggers the
release of Ca
2+
stored in the sarcoplasmic reticulum (calcium-
induced calcium release) by activating the
ryanodine recep-
tor (RyR).
The RyR is named after the plant alkaloid ryano-
dine that was used in its discovery. It is a ligand-gated Ca
2+

channel with Ca
2+
as its natural ligand. In skeletal muscle,
Ca
2+
entry from the extracellular fluid (ECF) by this route is
not required for Ca
2+
release. Instead, the DHPR that serves
as the voltage sensor unlocks release of Ca
2+
from the nearby
sarcoplasmic reticulum via physical interaction with the RyR.
The released Ca
2+
is quickly amplified through calcium-
induced calcium release. Ca
2+
is reduced in the muscle cell by
the sarcoplasmic or endoplasmic reticulum Ca
2+
ATPase
(SERCA) pump. The SERCA pump uses energy from ATP
hydrolysis to remove Ca
2+
from the cytosol back into the ter-
minal cisterns, where it is stored until released by the next
action potential. Once the Ca
2+
concentration outside the
reticulum has been lowered sufficiently, chemical interaction
between myosin and actin ceases and the muscle relaxes. Note
that ATP provides the energy for both contraction (at the
myosin head) and relaxation (via SERCA). If transport of
Ca
2+
into the reticulum is inhibited, relaxation does not occur
even though there are no more action potentials; the resulting
sustained contraction is called a
contracture.

TYPES OF CONTRACTION

Muscular contraction involves shortening of the contractile
elements, but because muscles have elastic and viscous ele-
ments in series with the contractile mechanism, it is possible

FIGURE 5–7

Flow of information that leads to muscle contraction.

Release of transmitter (acetylcholine)

at motor end-plate

Discharge of motor neuron

Generation of end-plate potential

Steps in contractiona

Binding of acetylcholine to nicotinic

acetylcholine receptors

Steps in relaxation

Increased Na+ and K+^ conductance

in end-plate membrane^

Generation of action potential

in muscle fibers

Inward spread of depolarization

along T tubules

Binding of Ca^2 + to troponin C,

uncovering myosin-binding

sites on actin

Formation of cross-linkages between

actin and myosin and sliding

of thin on thick filaments,

producing movement

Release of Ca^2 + from terminal

cisterns of sarcoplasmic reticulum

and diffusion to thick and

thin filaments

Ca^2 +^ pumped back into

sarcoplasmic reticulum

Release of Ca^2 +^ from troponin^

Cessation of interaction between

actin and myosin

aSteps 1–6 in contraction are discussed in Chapter 4.