Biomedical Engineering Reference
In-Depth Information
5.2.1.2
Transverse Tubules
Ventricular excitation-contraction coupling relies on sarcolemmal, transversely
oriented, deep, cylindrical invaginations — transverse (T) tubules — that are
juxtaposed beside terminal cisternae of the sarcoplasmic reticulum.
Excitation-contraction coupling actually requires Ca
2
+
ions. Calcium mediator
is mainly supplied by the sarcoplasmic reticulum that stores Ca
2
+
ions from
diastolic uptake for systolic release.
1
Sarcolemma repeatedly invaginates to form T tubules that plunge into the
sarcoplasma (Fig.
5.1
). Both sides of T tubules are close to the sarcoplasmic
reticulum. In addition, T tubules limit both ends of the sarcomere. Density of
T tubules influences Ca
2
+
influx. Transverse tubules allow to localize sarcolemmal
voltage-gated calcium channels and sarcoplasmic reticulum ryanodine receptors
2
into close proximity. Cardiac contraction actually results from opening of sarcolem-
mal voltage-gated calcium channels that are mostly located in T tubules. These
channels trigger Ca
2
+
influx with local accumulation that activates calcium release
from its sarcoplasmic reticulum stores, especially the close junctional regions of
this organelle. A decreased number of T tubules, particularly in atrial myocytes and
Purkinje cells, is correlated to local slow rate of Ca
2
+
ingress [
337
]. The dominant
Ca
2
+
ligand in the sarcomere is troponin-C attached to actin filaments.
Action potential sweeps quickly along the sarcolemma and T tubules to trigger
Ca
2
+
release from the sarcoplasmic reticulum. Owing to its speed, action potential
arrives almost simultaneously at all tubules of the T-tubule network to ensure that
all sarcomeres have a coordinated contraction. Calcium ions then diffuse to bind
to troponin.
3
This bond leads to the interaction between actin and myosin and
sarcomere contraction. When the process ends, Ca
2
+
is pumped back into the
sarcoplasmic reticulum (Sect.
6.6
).
The formation and maintenance of T tubules require myotubular myopathy
protein MTM1, or myotubularin-1 [
338
]. This phosphoinositide 3-phosphatase acts
on both phosphatidylinositol 3-phosphate and (3,5)-bisphosphate. Myotubularin
activity on PI(3)P and/or PI(3,5)P
2
may interfere with channel activaty.
On the other hand, atriomyocytes of many mammalian species do not express
extensive T-tubule networks. Coupling of Ca
V
channels and ryanodine receptors
occurs at dyadic junctions at the cell periphery. Peripheral Ca
2
+
ions do not
diffuse into the center of atriomyocytes. Three-dimensional non-junctional lattice
of ryanodine receptors may sense cortical Ca
2
+
signals and transmit them to
1
In the cytoplasm around myofibrils, free calcium concentration [Ca]
10
−
6
mol/kg and [Ca
2
+
]
∼
10
−
9
mol/kg. These amounts are insufficient for contraction. Calcium influx
∼
10
−
12
mol/cm
2
cannot explain contraction. Most Ca
2
+
comes from the sarcoplasmic reticulum (SR; SR [Ca
2
+
]
∼
10
3
sarcolemma [Ca
2
+
]) [
336
].
2
The plant Ryania speciosa ensures its defense against insects by producing the alkaloid ryanodine.
The latter binds specifically to Ca
2
+
-releasing channel of the sarcoplasmic reticulum Ca
2
+
store.
3
When [Ca
2
+
]
∼
Ca
2
+
binds
is high,
to troponin
that
then acts
on tropomyosin,
initiating
conformational changes.
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