Biomedical Engineering Reference
In-Depth Information
myocytes to contract in response to stretch. It actually couples the contraction-
relaxation state to smooth myocyte deformation with length-dependent changes
in contractility associated with possible modifications in ion channel activity,
cell membrane polarization, and/or cell metabolism [
788
]. It is characterized by
depolarization of the smooth myocyte plasma membrane and rise in intracellular
calcium concentration.
Stresses can actually act on: (1) plasmalemmal ion channels, exchangers, and
transporters and (2) membrane-bound enzymes that modulate activity of contractile
proteins. Stretch-activated channel gating depends on stresses transmitted by the
cytoskeleton.
Plasma Membrane Depolarization - Mechanosensitive Ion Carriers
Stretched smooth myocytes respond to pressure-dependent membrane depolariza-
tion associated with spike generation [
789
,
790
], the resting potential being mainly
determined by K
+
ions [
769
]. The membrane depolarization provokes a pressure-
induced myogenic contraction of arterial smooth muscle and reduces lumen caliber.
Stretch-activated calcium channels
70
Ca
2
+
]
i
,
71
that modulate intracellular
[
can
Ca
2
+
]
i
. Ligand-gated channels on SMC membrane
may be excited by vasomotor factors. Voltage-gated (K
V
)andCa
2
+
-activated
(K
Ca
)K
+
channels, especially large-conductance ones (BK), yield membrane
repolarization that counteracts effect of SMC stretch. Consequently, stretching
effect on SMC polarization is maintained in presence of inhibitors of K
Ca
channel,
due to activation by Ca
2
+
ions.
recruit Ca
V
channels to raise
[
Plasma Membrane Depolarization - Triggering Chemicals
On the other hand, Agent 20-hydroxyeicosatetraenoic acid, a metabolite of
arachidonic acid, can inhibit large conductance Ca
2
+
-activated K
+
channel [
794
].
Cerebral arterial myocytes synthesize cytochrome-P450-4A that catalyzes the
formation of 20HETE from arachidonic acid. The 20HETE production in cerebral
arterial
myocytes
increases
with
elevated
intravascular
pressure.
The
potent
vasoconstrictor
20HETE
activates
protein
kinase-C.
The
resulting
inhibition
of
BK
channels depolarizes arterial smooth muscle
cell
membrane, thereby
Ca
2
+
level,
activating
Ca
V
1
channel,
increasing
intracellular
and
priming
vasoconstriction [
795
].
70
Smooth myocytes can directly contract in response to stretch after activation of its stretch-
sensitive ion channels [
791
-
793
], contraction being maintained by a sustained deformation.
71
Plasmalemmal stretch-activated calcium channels on endothelial cells modulate
Ca
2
+
]
i
, from
[
which depend syntheses of vasomotor substances.
Search WWH ::
Custom Search