Biomedical Engineering Reference
In-Depth Information
Tabl e 9. 9.
Calcium channels and pumps of endothelial cells (Source: [
895
]). (
Part 1
)
Non-selective cation channels (NSC). Endothelial cells respond to most stimuli with a calcium
influx. The depolarizing action of Ca
2
+
influx is compensated by activation of Ca
2
+
-dependent
K
+
channels. In addition, non-selective cation channels, permeable to Ca
2
+
or not, can generate a
negative feedback on calcium influx by membrane depolarization.
Ion channels
Features
Purinoceptor
ATP and shear stress-induced
Ca
2
+
entry
(P2X
4
)
Na
+
,K
+
,andCa
2
+
permeability
Superoxide-gated NSC
Activation by PLC, IP
3
,andCa
2
+
Receptor-activated cation channels
(Ca
2
+
-permeable; RACC)
(positive feedback)
(TRP3/4/5/6 ?)
NOS3 stimulation
Amiloride-sensitive NSC
Blood-brain barrier
Negative feedback on Ca
2
+
influx
Cyclic nucleotide-activated NSC
CGN2
Activation by the NOS3-NO-cGMP axis
Hyperpolarization-activated
Blood-brain barrier
cyclic nucleotide-gated channels
NO- and cGMP-dependent cell processes
(HCN; Ca
2
+
permeable)
Modulation by NO, cGMP, and cAMP
(Cx37, Cx40, and Cx43) that are expressed in endothelial cells.
38
The electrical
coupling via high-conductance gap junctions between endothelial cells and smooth
myocytes is particularly important in arterioles.
9.5.4.1
Calcium Channels and Calcium Signaling
Calcium influx channels are important for long-lasting responses that are required
for the release of various compounds (e.g., nitric oxide, platelet-activating factor,
tissue factor pathway inhibitor, tissue plasminogen activator, and von Willebrand
factor; Sect.
9.8
;Tables
9.9
to
9.11
).
Two types of Ca
2
+
signals include: (1)
calcium oscillations
and (2)
biphasic
increase
in intracellular calcium level with a fast peak followed by a long-lasting
plateau. Fast transient Ca
2
+
peak is caused by IP
3
-induced Ca
2
+
release from
intracellular stores, whereas the plateau phase results from Ca
2
+
influx from the
extracellular space activated by store depletion.
Calcium oscillations are mainly due to periodic discharges of intracellular Ca
2
+
stores. They are triggered by low concentrations of ATP, acetylcholine, bradykinin,
histamine, and substance-P. Biphasic increase in intracellular calcium concentration
38
Connexin-43 is more abundant in macrovascular than in microvascular endothelia. Aortic
and pulmonary arterial endothelia express all three types of connexin, whereas coronary artery
endothelium expresses only Cx40 and Cx37. Gap junctions are made of same or different isoforms.
(only Cx40-Cx37 and Cx43-Cx37 complexes).
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