Biomedical Engineering Reference
In-Depth Information
filtration rate, hence supporting the tubuloglomerular feedback . Both secreted ATP
and its catabolite adenosine on afferent arteriole smooth myocytes cause vasocon-
striction upon binding to nucleoside (A 1 ) and nucleotide (e.g., P2X 1 ) receptors and
generating Ca 2 + signals [ 696 ]. An intercellular Ca 2 + wave through gap junctions
causes a coordinated contraction of both intra- and extraglomerular mesangial cells,
specialized smooth myocytes. Therefore, the tubuloglomerular feedback relies on
Ca 2 + waves primed by extracellular ATP that propagate from macula densa cells
toward proximal segments of the afferent arteriole and corresponding glomerulus
as well as all intraglomerular elements, including the most distant podocytes [ 696 ].
The strongest vasoconstriction occurs in the terminal, intraglomerular segment of
the afferent arteriole and propagates to proximal segments, thereby reducing the
glomerular filtration rate.
In addition, connexin-40 hemichannels, extracellular ATP, and P2 receptors
enable the motion of calcium waves in glomerular endothelial cells from a single
glomerular endothelial cell subjected to mechanical stimuli [ 697 ]. Hence, autoreg-
ulation that maintains renal blood flow and glomerular filtration rate involves a
propagating calcium wave in the juxtaglomerular apparatus via the release of ATP
and nucleotide signaling.
7.9.3.5
Pannexin Channels
Three pannexin isoforms exist (Panx1-Panx3). Whereas Panx1 and Panx3 may
assemble into hexamers, Panx2 may form heptamers or octamers. Once assembled
in the endoplasmic reticulum and Golgi body and transported to the plasma
membrane, they do not form gap junctions, but pannexin channels open to the
extracellular space. The latter is permeable to ATP messenger. They are observed
on glial cells and neurons in the central nervous system, T cells, airway epithelial
cells, red blood capsules, and vascular smooth muscle and endothelial cells [ 686 ].
Pannexin-1, but neither Panx2 nor Panx3, lodges in mouse thoracodorsal resistance
arteries [ 698 ]. Pannexins mediate paracrine communication via release of ATP or
UTP nucleotides.
Pannexin-1 channel in resistance arteries participates in the response triggered
by
1d-adrenergic receptor bound to noradrenaline liberated from nerve termi-
nals innervating the blood vessel wall that coordinates vascular smooth myocyte
contraction via release of ATP, a potent vasoconstrictor [ 698 ]. Pannexin-1 and
α
α
1d-
adrenoreceptor form a proteic complex.
7.10
Vascular Oxygen Sensing
Vascular oxygen sensors in smooth myocytes respond to changes in oxygen con-
centration by stimulating redox mediators that, in turn, regulate suitable effectors.
Vascular smooth myocytes use aerobic glycolysis that generates 2 mol of ATP per
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