ABSTRACT
The pulmonary vasculature mainly comprises vascular smooth muscle of the large vessel wall and endothelium of large and small vessels that arise from embryologically distinct origins. Whereas vascular smooth muscle cells generally control vascular tone, the endothelium is ametabolically active participant in the production of numerous vasoactive autacoids andparticipates in control of hemostasis, white blood cell trafficking, hormonemetabolism, permeability, vascular growth, and the balance between blood vessel survival and apoptosis. As in other cell systems, physiological transitions in cytosolic Ca2þ concentration ([Ca2þ]i) in smooth muscle and endothelium regulate a variety of critical cellular functions, ranging from contraction or shape change to secretion, endo-and exocytosis, cell growth, differentiation,modulation of enzyme function, and progression through the cell cycle. Within the same cell, Ca2þ influx (i.e., entry across the plasma membrane) represents an important signal that modulates each of these functions independently, under appropriate physiological conditions. To differentiate the Ca2þ signals required for these disparate functions, a complex network of ion channels has evolved inmammalian cells. Plasmalemmal Ca2þ channels can be broadly divided into voltage-gated and voltage-independent channels. The latter category includes receptor-operated and ligand-gatedCa2þ channels, capacitative or store-operatedCa2þ channels, and a variety of Ca2þ-permeable nonselective cation channels including mechanosensitive and cyclic nucleotide-gated channels.
