A calcium channel ‘guilty’ of pulmonary edema

A signalling cascade involving a calcium ion channel, which is highly expressed in the lung, is identified as being responsible for lung ischemia-reperfusion induced edema, reports Nature Communications this week. These findings highlight novel pharmacological targets that could potentially be used for the treatment of this condition. Lung ischaemia – reperfusion-induced edema is a life-threatening condition that can lead to lung failure. It is one of the most common causes of mortality after lung transplantation and acute lung embolism. A rise in the levels of reactive oxygen species and intracellular calcium concentration in endothelial cells, found in blood vessels, is thought to be the initial step in the development of lung injury which results in the abnormal accumulation of fluids and edema formation. Alexander Dietrich and colleagues generated mice, by bone marrow transplantation, to specifically delete proteins suspected to be involved in the loss of the endothelial cell barrier. They showed that the protein NADPH-dependent oxidase on endothelial cells is responsible for producing reactive oxygen species, which, in turn, set in motion a signalling cascade that results in the ultimate activation of the ion channel TRPC6. Activation of TRPC6 causes the influx of calcium into the endothelial cells thus rendering them more permeable and increasing the chance of edema formation. By uncovering the proteins involved in the initial steps of lung edema, the work may offer a promising strategy for combating this condition.

doi: 10.1038/ncomms1660

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