Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 951497, 16 pages
Review Article

Pathogenic Role of Store-Operated and Receptor-Operated Channels in Pulmonary Arterial Hypertension

1Section of Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Pharmacology, Institute for Personalized Respiratory Medicine, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL 60612, USA
2Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA

Received 17 May 2012; Revised 12 July 2012; Accepted 16 July 2012

Academic Editor: Jesus Garcia

Copyright © 2012 Ruby A. Fernandez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Pulmonary circulation is an important circulatory system in which the body brings in oxygen. Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness are the major causes for the elevated pulmonary vascular resistance (PVR) in patients with PAH. The elevated PVR causes an increase in afterload in the right ventricle, leading to right ventricular hypertrophy, right heart failure, and eventually death. Understanding the pathogenic mechanisms of PAH is important for developing more effective therapeutic approach for the disease. An increase in cytosolic free concentration ( ) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC migration and proliferation which lead to pulmonary vascular wall thickening and remodeling. It is thus pertinent to define the pathogenic role of signaling in pulmonary vasoconstriction and PASMC proliferation to develop new therapies for PAH. in PASMC is increased by influx through channels in the plasma membrane and by release or mobilization from the intracellular stores, such as sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). There are two entry pathways, voltage-dependent influx through voltage-dependent channels (VDCC) and voltage-independent influx through store-operated Ca2+ channels (SOC) and receptor-operated channels (ROC). This paper will focus on the potential role of VDCC, SOC, and ROC in the development and progression of sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in PAH.