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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1415-1459
Copyright ©2001 by the American Physiological Society
Department of Physiology, KU Leuven, Campus Gasthuisberg, Leuven, Belgium
Nilius, Bernd and
Guy Droogmans.
Ion Channels and Their Functional Role in Vascular
Endothelium. Physiol. Rev. 81: 1415-1459, 2001.
Endothelial cells (EC) form a unique
signal-transducing surface in the vascular system. The abundance of
ion channels in the plasma membrane of these nonexcitable cells has
raised questions about their functional role. This review presents
evidence for the involvement of ion channels in endothelial cell
functions controlled by intracellular Ca2+ signals, such as
the production and release of many vasoactive factors, e.g., nitric
oxide and PGI2. In addition, ion channels may be involved
in the regulation of the traffic of macromolecules by endocytosis,
transcytosis, the biosynthetic-secretory pathway, and exocytosis,
e.g., tissue factor pathway inhibitor, von Willebrand factor, and
tissue plasminogen activator. Ion channels are also involved in
controlling intercellular permeability, EC proliferation, and
angiogenesis. These functions are supported or triggered via ion
channels, which either provide Ca2+-entry pathways or
stabilize the driving force for Ca2+ influx through these
pathways. These Ca2+-entry pathways comprise
agonist-activated nonselective Ca2+-permeable cation
channels, cyclic nucleotide-activated nonselective cation channels,
and store-operated Ca2+ channels or capacitative
Ca2+ entry. At least some of these channels appear to be
expressed by genes of the trp family. The driving force for
Ca2+ entry is mainly controlled by large-conductance
Ca2+-dependent BKCa channels (slo),
inwardly rectifying K+ channels (Kir2.1), and at least two
types of Cl 
channels, i.e., the
Ca2+-activated Cl channel and the
housekeeping, volume-regulated anion channel (VRAC). In addition to
their essential function in Ca2+ signaling, VRAC channels
are multifunctional, operate as a transport pathway for amino acids and
organic osmolytes, and are possibly involved in endothelial cell
proliferation and angiogenesis. Finally, we have also highlighted the
role of ion channels as mechanosensors in EC. Plasmalemmal ion channels
may signal rapid changes in hemodynamic forces, such as shear stress
and biaxial tensile stress, but also changes in cell shape and cell
volume to the cytoskeleton and the intracellular machinery for
metabolite traffic and gene expression.
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