ABSTRACT

In biological systems, intracellular Ca2þ ions serve as a ubiquitous messenger for numerous cellular functions ranging from muscle contraction to gene expression. Ca2þ signals are generated by multiple specific Ca2þ

transporters, delivered globally or locally, and decoded by various effectors according to the signal amplitude and frequency in their immediate vicinities (1). In pulmonary vascular smooth muscle, major attention has been focused on the global elevation of [Ca2þ]i, because it is responsible for the initiation of actin-myosin interactions during smooth muscle contraction. However, due to the spatial distribution of different Ca2þ

transporters, the diffusion kinetics of Ca2þ ions, and the subcellular microarchitecture, heterogeneity in local [Ca2þ] is expected. It has been estimated on theoretical grounds that [Ca2þ] can exceed 100 mM in the vicinity (Ca2þ microdomain) of an open Ca2þ conducting channel (2). Such large local gradients of [Ca2þ] can provide fast and specific Ca2þ

signals to neighboring effector molecules to trigger Ca2þ-dependent processes that may not be responsive to global submicromolar increase in [Ca2þ]i.