Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 65

Plasma membrane deformability of red blood cells results from the coupling
between the phospholipid bilayer and spectrin network. Adenosine triphosphate
favors dynamical fluctuations in the RBC membrane [ 117 ]. Membrane vibrations
(amplitude

[10 nm]) that use both metabolic and thermal energies are enhanced at
the scale of spectrin mesh size to maintain the biconcave shape. Phosphorylation-
dependent binding of the cytoskeleton to the plasma membrane can explain the
correlation between dynamical fluctuations and biconcave shape. The spectrin
mesh-membrane binding creates these dynamical vibrations via local remodeling
of the spectrin junctions.

O

3.5.3.3 Pannexon and ATP Release

Erythrocytes express pannexin-1 that forms a mechanosensitive, ATP-permeable
channel ( pannexon ) in the plasma membrane [ 118 ]. These capsules release ATP
in response to hypoxemia (Sect. 9.10.9 ) as well as shear stress.
Adenosine triphosphate is an intra- and extracellular regulator. Red blood
capsules succor blood pressure regulation, as they release ATP, a paracrine mes-
senger that functions as a vasodilator, especially in arterial constrictions. It causes
vasodilation by releasing nitric oxide from endothelial cells.
The release of ATP is delayed with respect to the onset of increased shear
stress [ 119 ]. Remodeling of the spectrin-actin cytoskeleton network may launch
the mechanosensitive (deformation-triggered) ATP release; a shear-dependent mem-
brane viscosity may control the rate of release.
Flow-induced RBC deformation releases ATP that enables platelet adhesion
to the endothelium. Adenosine triphosphate behaves as a platelet inhibitor below
0.16 amol per platelet; 28 above this threshold, ATP is a platelet activator [ 120 ]. On
the one hand, ATP stimulates the production of nitric oxide in endothelial cells via
P2Y receptors and platelets; NO is vasodilator and platelet inhibitor. On the other,
ATP activates platelet ATP-gated P2X 1 ion channel, thereby causing a rapid Ca 2 +
entry that enables platelet aggregation. In particular, mild platelet stimulation with
low concentrations of collagen rapidly releases ATP that primes the P2X 1 -Ca 2 + -
PKC-ERK2 pathway [ 121 ]. This event enhances further degranulation, thereby
allowing complete platelet aggregation.
Proinsulin C-peptide increases glucose uptake by RBCs, intracellular Ca 2 +
concentration, and, subsequently, ATP release [ 122 ]. 29

28 Metric prefix symbol a for atto means 10 − 18 .
29 Preproinsulin contains an A- and B-chain, a connecting peptide (C-peptide), and a signal
sequence. It is processed by peptidases to proinsulin by removal of the signal peptide. Proinsulin
gives rise to insulin by elimination of the central C-peptide; both ends (A- and B-chain) remain
connected by disulfide bonds. Proinsulin C-peptide produced with insulin facilitates assembly,
folding, and processing of insulin in the endoplasmic reticulum. Equimolar amounts of C-peptide
and insulin are then stored in secretory granules of pancreatic β cells. Both can be released to

-Cell granules contain Zn 2 + transporter proteins; in these granules, Zn 2 + - the portal circulation. β