Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 463

EC

ER Ca

BM

NOS3
PLA2

IP3R

IEL

Ca pulsar

Ca

KCa3.1

MEJ

K

GJ

VDCC

SMC Ca spark

Kir2.1

−

RR

Ca

Ca

hyperpolarization

Ca

vasodilation

Fig. 9.1 Intercellular functional unit of the myoendothelial junction (MEJ; Source: [ 860 ]).
Myoendothelial junction is an endothelial domain that crosses the basement menbrane (BM)
and internal elastic lamina (IEL) to reach adjacent smooth myocyte membrane. The intercellular
functional unit is composed of: (1) connexins that form gap junctions (GJ); (2) inositol tris-
phosphate receptors (IP 3 R) and calcium-sensitive K Ca 3.1 channels (IK) in endothelial cell (EC);
and (3) inward rectifier potassium channels (K IR 2.1) and voltage-dependent calcium channels
(VDCC; Ca V 1.2) in smooth myocytes (SMC). Calcium pulsar is an endothelial Ca 2 + signal
that has a restricted localization to MEJ. Its activity is regulated by biological and mechanical
agents. Other endothelial calcium-dependent enzymes (e.g., endothelial nitric oxide synthase
[NOS3] and phospholipase-A2 [PLA2]) can be activated by calcium pulsars or waves. In smooth
myocytes, calcium sparks from clusters of ryanodine receptors of the endoplasmic reticulum
closely juxtaposed to the plasma membrane activate Ca 2 + -sensitive, large-conductance K Ca 1.1
channels, thereby causing a transient hyperpolarization that promotes vasodilation.

An increase in cytosolic Ca 2 + concentration in endothelial cells serves as a
vasodilatory signal, whereas, in smooth myocytes, it triggers vasoconstriction by
targeting the actin-myosin stress fibers.
In smooth myocytes, elementary calcium release ( calcium sparks ) from clusters
of ryanodine receptors of the endoplasmic reticulum closely juxtaposed to the
plasma membrane activate calcium-sensitive large-conductance K Ca 1.1 channels,
thereby causing a transient hyperpolarization that reduces vasoconstriction.
Calcium ion can also be locally released through inositol trisphosphate receptors
of endothelial endoplasmic reticulum to create the so-called endothelial calcium
pulsars in myoendothelial junctions to transmit vasoregulatory signals [ 860 ].
Calcium pulsars that encode signals between vascular endothelial cells and smooth
myocytes differ from Ca 2 + sparks generated by ryanodine receptors. One target
of calcium pulsars is K Ca 3.1 channels in endothelial projections to relax adjoining
smooth myocytes.
An intercellular functional unit can thus be defined that is composed of:
(1) connexins that form gap junctions; (2) endothelial IP 3 Rs and K Ca 3.1 channels;
and (3) inward rectifier K IR 2.1 channels and voltage-dependent Ca V 1.2 channels in
smooth myocytes (Fig. 9.1 ).