Biomedical Engineering Reference
In-Depth Information
head
Myosin
S1
actin
ATP
neck
S2
MHC
tail
regulatory MLC
essential MLC
Fig. 5.4 Myosin filaments (MHC: myosin heavy chain, MLC: myosin light chain). The neck has
binding sites for light chains, and the head for ATP and actin. For example, myosin-2 consists
of 2 head segments: S1, composed of heavy chains, connected to a long dimeric rod by a flexible
coiled-coil segment S2 (S2
-myosin-2). The coiled-coil light meromyosin rod tails of myosin-
2 are packed side by side, whereas both heads point away from the myosin filament surface (or light
meromyosin dimer axis). S1 subfragments act as ATP-driven motors, the conformation and actin
affinity of which change according to the status of ATPase sites. Actomyosin cross-bridges use
chemical energy liberated by the hydrolysis of cardiac actomyosin Ca 2 + -stimulated MgATPase.
δ
in
β
Myomesin acts for lateral registration. This structural protein of the M line assists
titin and myosin in the maintenance of their three-dimensional structure.
Cardiac myosin isoform-5.1 has higher ATPase and contractile activities than
isoform-5.3 [ 362 ]. Myosin isoforms may have a heterogeneous regional distribution.
5.3.3
Actin Thin Filaments
The thin filament (diameter
5 nm) is composed of actin , with small amounts of
2 regulatory proteins, troponin (TN) and tropomyosin (TMy, ). 32 Actin filaments
extend in direction normal to the Z lines from each side. They create the I band
where they do not overlap the thick filaments.
Heterodimeric troponin is composed of 3 subunits: TnC, TnI, and TnT. Troponin-
C has a binding site for Ca 2 + (calcium receptor/handling protein). Troponin-I 33
inhibits actin-myosin binding in the absence of Ca 2 + ion. Troponin-I is regulated by
32
: belt. G actin polymerizes in the presence of Ca 2 + ,Mg 2 + , and ATP to form F actin in a
double-helix chain with a pitch length of 35-36 nm. One tropomyosin runs in the groove of F actin.
One troponin exists for each tropomyosin.
33 Troponin-I has a key role in ischemia-induced contractile dysfunction. Ischemia leads to
intracellular acidosis. Troponin-I modifies the Ca 2 + sensitivity of actin. The fetal cardiac isoform
of troponin-I protects more from acidosis than the adult cardiac isoform, enhancing Ca 2 + activation
of sarcomere activity. The composition of troponin-I thus affects cardiac performance [ 363 ].
τρ
o
π
o
σ
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