Abstract
Transient receptor potential (TRP) genes represent a novel class of genes that are generally believed to encode for nonselective cation channels. A subfamily of TRP channels, canonical TRP (TRPC), which are highly permeable to Ca2+ (and Na+), co-assembles with each other to form functional store- and receptor-operated Ca2+ channels. TRPC mRNA and protein have been identified in pulmonary arterial smooth muscle and endothelial cells. The currents generated by Ca2+ influx through store- and receptor-operated Ca2+ channels have also been extensively characterized in these cells. More recently, the attention has shifted to identify the TRP subunits that underlie the function of native channels in the pulmonary vasculature, with the understanding that TRP channels assemble as either homo-or heterotetramers in vivo. This work in progress has yielded exciting information regarding the involvement of TRP channels in the control of smooth muscle contraction, and cell proliferation and migration. In this review, the authors focus on describing the function and transcriptional regulation of TRP proteins, and the store- and receptor-operated Ca2+ channels for which they are responsible, in pulmonary artery smooth muscle cells (PASMC). They also identify some key TRP proteins whose role in the pulmonary vasculature has been established, as well as some more novel subunits whose role, although intriguing, can only be inferred from other vascular studies. Finally, they describe the involvement of TRP channels in regulating pulmonary vasoconstriction, PASMC proliferation, and pulmonary endothelial barrier function.
We apologize to authors whose work was not cited here due to space restrictions. This work was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL 066012, HL 054043, and HL 064945).