Biomedical Engineering Reference
In-Depth Information
Tabl e 9. 1.
Mechanisms of endothelium-derived hyperpolarization (Source: [
856
]). Endothelium-
derived hyperpolarization (EDH) relies, at least partly, on cytosolic calcium influx upon liganded
receptors and/or hemodynamic stresses and activation of potassium channels, such as small,
intermediate, and, in some cases, large-conductance calcium-activated potassium channels (EC:
endothelial cell; MEES: myoendothelial microdomain extracellular space; SMC: smooth myocyte.
Diffusible factors
Potassium ion
Efflux from EC to MEES through K
Ca
and activation of SMC Na
+
-K
+
AT P a s e
and K
IR
channel
(transient, localized cue)
Epoxyeicosatrienoic acids
Opening of EC and SMC K
Ca
1.1 (BK),
Ca
2
+
entry through TRPV4
(EETs)
Hydrogen peroxide
Vasoconstriction, activation of
(H
2
O
2
)
SMC K
Ca
,K
AT P
,
and Na
+
-K
+
ATPase; no effect on EDH
in human radial and subcutaneous arteries
C-type natriuretic peptide
Vasorelaxation, activation of NP
2
(CNP)
and NP
3
receptors; role questionable
Contact-mediated mechanisms - Gap junctions
Electrochemical coupling
Eventual modulation by K
+
, EETs,
H
2
O
2
,CNP
direct coupling between endothelial and smooth muscle cells via myoendothelial
gap junctions (contact mechanism) and activity of ion carriers located in myoen-
dothelial microdomains (diffusible endothelial factor release; Table
9.1
).
Myoendothelial projections (MEP) contain myoendothelial gap junctions com-
posed of connexins, thereby enabling direct signaling between vascular endothelial
cells and smooth myocytes. Endothelial hyperpolarization is directly transmitted
to adjacent smooth myocyte via the myoendothelial gap junction. Endothelium-
dependent hyperpolarization of adjacent smooth myocytes closes their Ca
V
1.2
channel.
Hydrogen peroxide (H
2
O
2
) can influence gap junctional coupling in addition
to modulating the sensitivity of the contractile apparatus to calcium and activating
smooth muscle Na
+
-K
+
AT P a s e a n d B K
Ca
and K
AT P
channels [
856
]. However,
H
2
O
2
does not play a significant role in endothelium-dependent hyperpolariza-
tion [
857
].
Endothelium-dependent hyperpolarization factors (EDHF) comprise actions
K
+
of
ion,
nitric
oxide,
prostaglandins,
cytochrome-P450 products
epoxye-
icosatrienoic
acids,
and
myoendothelial
electrical
coupling,
but
is
neither
prostacyclin nor nitric oxide.
Two types of Ca
2
+
-activated K
+
channels are involved in endothelium-
dependent hyperpolarization (Table
9.2
): (1) small conductance Ca
2
+
-activated
K
+
channels (SK or K
Ca
2.3) that are widely distributed over the endothelial plasma
membrane and (2) intermediate conductance Ca
2
+
-activated K
+
channels (IK or
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