Biomedical Engineering Reference
In-Depth Information
than that of Ca
V
1.2 channel. However, Na
+
-Ca
2
+
exchangers can induce a Ca
2
+
influx able to trigger release of Ca
2
+
from the sarcoplasmic reticulum [
446
].
Furthermore, Na
+
-Ca
2
+
exchangers have limited activity, because the intracellular
Na
+
concentration decays during depolarization.
In cardiomyocytes,
phospholemman
86
regulates Na
+
-Ca
2
+
exchangers NCX1
and Na
+
-K
+
ATPases, hence Na
+
-Ca
2
+
-exchange (
i
NaCaX
)andNa
+
-K
+
-pump
(
i
NaK
AT P
) currents. Phosphorylated phospholemman (Ser68) disinhibits Na
+
-
K
+
ATPase, but mainly inhibits NCX1 [
447
]. Association of phospholemman
with Na
+
-K
+
ATPase does not require NCX1 exchanger. Phospholemman is
phosphorylated in response to
β
-adrenergic stimulation. Under stress conditions
with high [Na
+
]
i
,
β
-adrenergic-induced phosphorylation of phospholemman causes
a reduction in inotropy due to the relief of inhibition of Na
+
-K
+
AT P a s e [
448
].
5.10.3
Myocardial Calcium Channels
5.10.3.1
Voltage-Gated Calcium Channels
Cardiomyocytes possess 2 classes of voltage-gated Ca
2
+
channels: Ca
V
1.2 (L-type)
and Ca
V
3 (T-type). Although these Ca
2
+
channels have similar unitary Ca
2
+
conductances, Ca
V
1.2 trigger more efficiently cardiomyocyte contraction. Calcium
influx through Ca
V
1.2 produces greater amplitude and faster contractions.
Ca
V
1.2a
Channel Ca
V
1.2a
87
localizes mainly to junctions between the sarcolemma and
sarcoplasmic reticulum close to ryanodine receptors. Many of the Ca
V
1.2 channels
reside in T tubules.
Channel Ca
V
1.2 is composed of several types of subunits: a pore-forming
α
1
and auxiliary
β
,
γ
,and
α
2
δ
subunits (
α
2
δ
1-
α
2
δ
4), in addition to channel-resident
1
88
is not necessary to direct the plasmalemmal
Ca
V
1.2 density, but boosts its activation and inactivation kinetics.
Channel Ca
V
1.2 triggers Ca
2
+
-induced Ca
2
+
release from the junctional
sarcoplasmic reticulum through Ca
V
1.2-coupled ryanodin recptors (Ca
V
1.2-RyR
couplon
). A single small cluster of Ca
V
1.2 channels provokes a local Ca
2
+
sparklet
that activates a small cluster of closely apposed ryanodine receptors on
the sarcoplasmic reticulum membrane to create a Ca
2
+
spark
. The synchronous
occurrence of multiple Ca
2
+
sparks in the entire cardiomyocyte after action potential
arrival causes a massive release of Ca
2
+
from the sarcoplasmic reticulum to trigger
contraction.
calmodulin [
449
]. Subunit
α
2
δ
86
A.k.a. FXYD domain-containing ion transport regulator-1 (FXYD1).
87
A.k.a. dihydropyridine receptors.
88
Subunit
α
2
δ
1 is also synthesized at high levels in vascular smooth myocytes.
Search WWH ::
Custom Search