ABSTRACT
Pulmonary artery tone is controlled by both the membrane potential of pulmonary artery smooth muscle cells (PASMCs) and a variety of circulating and locally released mediators (1-3). Vascular tone is mainly dependent on the value of the cytoplasmic calcium concentration ([Ca2þ]i), which is generally considered the main factor controlling the activation process of smooth muscle contraction (4,5). Agonists can thus positively or negatively modulate pulmonary tone by acting on the calcium signaling pathway. An increase in [Ca2þ]i can result from an influx of extracellular calcium, a release of intracellular stored calcium, or a decrease of calcium efflux and reuptake (6). Extracellular calcium ions enter the smooth muscle cells mainly following the activation of voltage-gated calcium channels (L-type calcium channels), receptor-operated channels, or store-operated channels, whereas intracellular calcium originates mainly from the sarcoplasmic reticulum (SR) via the activation of two types of receptors or channels: the inositol 1,4,5 trisphosphate receptor=channel (RIP3) and the ryanodine receptor=channel (RyR) (7,8). However, the kinetics, the pattern of [Ca2þ]i increase, and its temporal correlation with the contractile response are not yet clearly understood. Techniques such as enzymatic isolation of smooth muscle cells, microspectrofluorimetry (using fluorescent indicators such as indo1, fura 2, fluo 3),
allowing measurement of the [Ca2þ]i in single cells, sometimes combined with electrophysiological (patch-clamp) experiments, are now widely used and have brought about new and important information in the field of cellular calcium signaling and the control of the [Ca2þ]i by agonists.
