Decoding dynamic Ca(2+) signaling in the vascular endothelium

Although acute and chronic vasoregulation is inherently driven by endothelial Ca(2+), control and targeting of Ca(2+)-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca(2+) events comprising an intricate signaling network along the vascular intima. Discrete Ca(2+) transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K(+) channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca(2+) elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca(2+) signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca(2+) dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis.