CHAPTER 3 • CELLULAR STRUCTURE AND FUNCTION
the myocyte action potential, calcium entry
into the cell diminishes and the sarcoplas-
mic reticulum sequesters calcium by an ATP-
dependent calcium pump, sarcoendoplasmic
Fig. 3-3). As intracellular calcium concentra-
tion declines, calcium dissociates from TN-C,
which causes a conformational change in the
troponin-tropomyosin complex; this again
leads to troponin-tropomyosin inhibition of
the actin-binding site. At the end of the cycle,
a new ATP binds to the myosin head, displac-
ing the adenosine diphosphate, and the ini-
tial sarcomere length is restored. Thus, ATP
is required both for providing the energy of
contraction and for relaxation. In the absence
of sufficient ATP as occurs during cellu-
lar hypoxia, cardiac muscle contraction and
relaxation will be impaired. The events associ-
ated with excitation-contraction coupling are
summarized in Table 3-1.
Regulation of Contraction
Several cellular mechanisms regulate contrac-
tion (Fig. 3.5). Most of these mechanisms
SUMMARY OF EXCITATION-
1. Ca++ enters cell during depolarization
and triggers release of Ca++ by terminal
2. Ca++ binds to TN-C, inducing a
conformational change in the troponin
3. Myosin heads bind to actin, leading to
cross-bridge movement (requires ATP
hydrolysis) and reduction in sarcomere
4. Ca++ is resequestered by sarcoplasmic
reticulum by the SERCA pump.
5. Ca++ is removed from TN-C, and myo-
sin unbinds from actin (requires ATP);
this allows the sarcomere to resume its
original, relaxed length.
ATP, adenosine triphosphate; SERCA, sarcoendoplasmic
reticulum calcium ATPase; TN-C, troponin-C.
ultimately affect calcium handling by the cell.
Changes in contraction resulting from altered
calcium handling and myosin ATPase activity
are referred to as inotropic changes (inotropy).
Inotropy is modulated by (1) calcium entry
Ofi fin 11
■ FIGURE 3.4 Sarcomere shortening and the sliding filam ent theory. Calcium binding to TN-C permits
actin-m yosin binding (cross-bridge form ation) and ATP hydrolysis. This results in the thin filaments slid-
ing over the myosin during cross-bridge cycling, thereby shortening the sarcomere (distance between
Z-lines). Removal of calcium from the TN-C inhibits actin-m yosin binding so that cross-bridge cycling
ceases and the sarcomere resumes its relaxed length.