Biomedical Engineering Reference
In-Depth Information
Table 6.19.
Main calcium-handling proteins in cardiomyocytes. The intracellular calcium con-
centration is
regulated by ion carriers and intracellular Ca
2
+
-binding proteins.
Ca
V
1
Influx across sarcolemma
Contraction (inotropy)
RyR
Release from SR
Contraction
Ca
2
+
binding
Troponin-C
Contraction
Ca
2
+
binding
Calmodulin
Influx limitation
NCX
Influx across sarcolemma
Contraction
Na
+
]
i
)
Efflux across sarcolemma
[
(high
Relaxation
Ca
2
+
]
i
)
(high
[
SERCA
SR sequestration
Relaxation (lusitropy)
Calsequestrin
Storage
Relaxation
Calcium ions are a major factor with ATP in cardiac excitation-contraction
coupling. Calcium influx from the extracellular medium and mainly cellular stores
to the sarcomere, together with ATP from cytolosic sources and mitochondria, as
well as outflux from the sarcomere to the sarcoplasmic reticulum, mitochondria,
and extracellular fluids are strongly regulated. Moreover, effects influence causes.
The membrane potential modulates Ca
2
+
transport that, in turn, modifies the
membrane potential.
The magnitude and duration of myocyte contraction is regulated by [Ca
2
+
]
i
that depends on protein carriers on cell and sarcoplasmic reticulum membranes
(Fig.
5.16
,Tables
5.9
and
6.19
). Four main Ca
2
+
compartments exist in the cardiac
micropump: (1) the extracellular space; (2) sarcoplasmic reticulum for capture and
release; (3) troponin-C transiently; and (4) calmodulin. Oxygen is the combustible
molecule. Cytoplasmic [Ca
2
+
]
i
(hence CMC contraction-relaxation) is strongly
controlled.
During the systole, 2 mechanisms - voltage-sensitive release and Ca
2
+
-induced
Ca
2
+
release - induce Ca
2
+
flux from the sarcoplasmic reticulum via ryanodine
channels (SR Ca
2
+
release channels) [
636
]. The voltage-sensitive release mecha-
nism is activated by a potential of about
60 mV and triggers Ca
2
+
release from
the sarcoplasmic reticulum into the cytoplasm. Calcium-induced Ca
2
+
release deals
with Ca
2
+
flux through Ca
V
1 channels that elicits Ca
2
+
release from ryanodine
channels. Influx of Ca
2
+
from the sarcoplasmic reticulum sufficiently increases the
cytosolic [Ca
2
+
]
i
to cause contraction.
67
Na
+
-Ca
2
+
porter which exchanges 3 Na
+
for 1 Ca
2
+
operates during phase 2. It stabilizes intracellular [Ca
2
+
]
i
by a repeated
entry of Ca
2
+
.
Relaxation requires Ca
2
+
removal from the cytosol. During the relaxation,
cytosolic [Ca
2
+
]
i
decreases due to Ca
2
+
uptake: (1) into the sarcoplasmic reticu-
lum via sarco(endo)plasmic reticulum Ca
2
+
AT P a s e s a n d N a
+
-Ca
2
+
exchangers;
−
67
About 10% of the calcium needed for cardiac contraction enters from the extracellular space.
This trigger calcium induces release of the remainder from the sarcoplasmic reticulum.
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