Role of Ion Channels in Ductus Arteriosus Closure

Abstract

The Ductus Arteriosus (DA) is a normal and essential fetal structure that connects the main pulmonary artery and the descending aorta. The DA constriction which occurs immediately after birth is triggered by: (a) an increase in oxygen tension, (b) a dramatic decline in circulating PGE2 and a promotion of its degradation in the lung, (c) a decrease in the expression of PGE receptors in the DA wall and (d) a decrease in blood pressure within the DA. Ion channels play an essential role in this acute response that is known as functional DA closure. Oxygenation from fetal to neonatal circulation inhibits several potassium channels (voltage-dependent and ATP-dependent), which then leads to membrane depolarization. This depolarization triggers the activation of voltage-dependent calcium channels, and extracellular calcium then enters into the cytosol of smooth muscle cells of the DA. Calcium is also released from the sarcoplasmic reticulum, with a consequent supply provided through store-operated calcium channels. An increase in cytosolic calcium induces DA constriction. Ion channels also play a role in vascular remodelling of the DA, although this has not yet been extensively investigated. Voltage-dependent L- and T-type calcium channels promote formation of intimal thickening through an increase in proliferation and migration of DA smooth muscle cells. Current medical treatment for patients with persistent patent DA is limited to cyclooxygenase inhibitors such as indomethacin and ibuprofen. A better understanding of the role of ion channels in vasoconstriction and vascular remodelling of the DA may encourage the design and development of novel pharmacological treatments for patients with patent ductus arteriosus. In this review, we focus on current knowledge on the roles of ion channels in the DA.