Introduction

Calcium is an important trigger and regulator of endothelial cell physiology. Historically, most information has come from the study of endothelial cells in culture, chiefly cells from large vessel endothelia such as aorta and umbilical vein. More recently, cultured microvascular endothelial cells have been investigated, and some studies have been done on endothelial cells in intact and split-open vessels, or covering the surface of cardiac valves. Studies on brain microvascular endothelium have begun more recently. This chapter reviews studies on the mechanisms governing changes in intracellular calcium involved in the normal physiology of systemic endothelium, evidence that calcium contributes to the control of endothelial permeability in both non-brain and brain endothelium, and cellular mechanisms demonstrated in brain microvascular endothelial cells.

Mechanisms controlling elevation of intracellular calcium in mammalian cells

Cytoplasmic free calcium controls a large number of cellular functions, from the activation of enzymes, to secretory processes and contraction. In mammalian cells, elevation of intracellular calcium occurs from two sources: Ca2+ release from intracellular stores, and Ca2+ influx across the plasma membrane. Two major classes of tetrameric calcium channels control intracellular calcium release, the ryanodine receptor (RR), and the inositol trisphosphate receptor (InsP3R) (Berridge, 1993). In skeletal muscle, the RR is directly coupled to dihydropyridine receptors in the T-tubular plasmalemma, so that membrane depolarization during an action potential leads to intracellular calcium release.