The role of intracellular ion channels in regulating cytoplasmic calciumin pulmonary arterial mmooth muscle: which store and where?

The mobilisation of intracellular Ca(2+) stores plays a pivotal role in the regulation of arterial smooth muscle function, paradoxically during both contraction and relaxation. Moreover, different spatiotemporal Ca(2+) signalling patterns may trigger differential gene expression while mediating the same functional response. These facts alone serve to highlight the importance of the growing body of evidence in support of the view that different Ca(2+) storing organelles may be selected by the discrete or co-ordinated actions of multiple Ca(2+) mobilising messengers. In this respect, it is generally accepted that sarcoplasmic reticulum stores may be mobilised by the ubiquitous messenger inositol 1,4,5 trisphosphate. However, relatively little attention has been paid to the role of Ca(2+) mobilising pyridine nucleotides in arterial smooth muscle, namely cyclic adenosine diphosphate-ribose and nicotinic acid adenine dinucleotide phosphate. This review will, therefore, focus on the role of these novel Ca(2+) mobilising messengers in pulmonary arterial smooth muscle, with particular reference to hypoxic pulmonary vasoconstriction.