Biomedical Engineering Reference
In-Depth Information
Ca
α 1AR
β 2AR
BK
VGCC
NO
PLC
K
Ca
−
cAMP
PKG
IP3
DAG
SERCA2
RC
Ca
ER
PKC
PKA
IP3R
PAK
CamK
Ca
Cam
MLCK−P
MLCK−Ca−Cam
MLCK
contraction
MLC−P
MLC
Rho
MLCP
RoCK
ILK
SMC
GEF
I
ATR
Fig. 7.7
Contraction of the vascular smooth myocyte and its regulation (Source: [
650
]; BK: large-
conductance Ca
2
+
-activated K
+
channel; Cam: calmodulin; DAG: diacylglycerol; GEF: GDP-to-
GTP-exchange factor; IP
3
(R): inositol trisphosphate (receptor); I: integrin; PKA, PKC: protein
kinase-A, -C; PLC: phospholipase-C; VGCC: L-type voltage-gated Ca
2
+
channel [Ca
V
1.2]).
Adrenergic receptors-
2AR) cause contraction via the PLC-PKC pathway
and relaxation via the cAMP-PKA cascade, respectively. The myosin light chain kinase (MLCK)
can be phosphorylated by PKA, PKC, CamK2, and PAK kinases. Myosin light chain phosphatase
(MLCP) can be phosphorylated by RoCK and ILK kinases. Phosphorylation of MLCK, which
requires Ca
2
+
-Cam, leads to activation, whereas MLCP phosphorylation leads to inactivation.
Calcium ATPase SERCA2 is targeted by PKA, ryanodine-sensitive channel (RC) with its
regulatory protein FKBP and IP
3
R are activated by PKA, PKC, or CamK2 kinase. Nitric oxide-
induced PKG inhibits Ca
V
1.2 channel and activates BK channel.
α
1(
α
1AR) and -
β
2(
β
Tabl e 7. 7.
Contraction and relaxation features in the cardiomyocyte and smooth myocyte. The
cardiomyocyte is characterized by fast, reversible calcium binding to cardiac troponin-C. Smooth
myocyte activity is regulated by reversible phosphorylation of myosin and/or actin components.
Vasomotor tone depends on the activity ratio between MLCK and MLCP.
-Adrenergic receptor
signaling increases intracellular calcium concentration in the cardiomyocyte, whereas its activity
in vascular smooth myocyte is independent of calcium.
β
CMC
SMC
Contraction/relaxation
Fast
Slow
ATP consumption
High
Low
β
-Adrenergic signaling
I
+
Relaxation
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