Biomedical Engineering Reference
In-Depth Information
The combined compliance of titin inside cardiomyocytes and of collagen
network surrounding cardiomyocytes enables sarcomere stretch during diastole.
During relaxation, sarcomere length and [Ca
2
+
]
i
remain constant.
6.6.1
Intercellular and Cell-Matrix Adhesions
Mechanosensitive adhesions between cardiomyocytes enable their functioning as
an electromechanical syncytium. In the adult heart, healthy ventriculomyocytes
are characterized by cell-matrix adhesions at their sides (transversal edges) and
intercellular junctions at axial ends (between-cell interfaces) [
635
].
Focal adhesions stabilize cardiomyocytes between them and to the matrix during
assembly of sarcomeres and intercalated discs. During maturation of intercalated
discs of cardiomyocytes subjected to cyclic loadings, focal adhesions disassem-
ble [
635
].
6.6.2
Troponins and Tropomyosin
Cardiomyocyte contraction and relaxation are effected by cyclic association and
dissociation of actin and myosin. This cycle is regulated by Ca
2
+
, the troponin
complex, and tropomyosin. Troponin-C binds Ca
2
+
, troponin-I links to actin and
blocks interaction with myosin when [Ca
2
+
]
i
is low, and troponin-T connects to
tropomyosin. When [Ca
2
+
]
i
rises (mainly after Ca
2
+
release from the sarcoplasmic
reticulum through voltage-dependent Ca
2
+
channels is insufficient to cause con-
traction), Ca
2
+
binds to troponin-C. The Ca
2
+
-TnC complex moves TnI away from
myosin-binding sites on actin, alters the interaction between TnT and tropomyosin,
and frees the binding sites between myosin and actin to initiate a new cross-bridge
cycle at many points along the filament, which promotes contraction. Supply of ATP
yields energy for contraction. Hydrolysis of ATP stops as soon as Ca
2
+
is removed
from cytosol.
6.6.3
Calcium Ion and Its Partners
Heart inotropy depends on intracellular (cytosolic) Ca
2
+
concentration and
sensitivity of contractile proteins to Ca
2
+
ions. A maximal stress of about 1 kPa
suffices to generate the systolic pressure in the normal left ventricle for blood
ejection into aorta [
328
]. In fact, 4 major factors dictate the active force: [Ca
2
+
]
i
,
phosphorylation status of troponin, sarcomere length, and velocity of sarcomere
shortening.
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