The Role of Ion Channels in Hypoxic Pulmonary Vasoconstriction

VA Medical Center, 1 Veterans Drive, 111C, Minneapolis, MN, 55417, USA.
Advances in Experimental Medicine and Biology (Impact Factor: 1.83). 01/2010; 661:3-14. DOI: 10.1007/978-1-60761-500-2_1
Source: PubMed

ABSTRACT Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which localized flow of blood in small resistance pulmonary arteries is matched to alveolar ventilation. This chapter discusses the role of several potassium and calcium channels in HPV, both in enhancing calcium influx into smooth muscle cells (SMCs) and in stimulating the release of calcium from the sarcoplasmic reticulum, thus increasing cytosolic calcium. The increase in calcium sensitivity caused by hypoxia is reviewed in Chapter 19. Particular attention is paid to the activity of the L-type calcium channels which increase calcium influx as a result of membrane depolarization and also increase calcium influx at any given membrane potential in response to hypoxia. In addition, activation of the L-type calcium channel may, in the absence of any calcium influx, cause calcium release from the sarcoplasmic reticulum. Many of these mechanisms have been reported to be involved in both HPV and in normoxic contraction of the ductus arteriosus.

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    ABSTRACT: Significance: An acute lack of oxygen in the lung causes hypoxic pulmonary vasoconstriction, which optimizes gas exchange. In contrast, chronic hypoxia triggers a pathological vascular remodeling causing pulmonary hypertension, and ischemia can cause vascular damage culminating in lung edema. Recent advances: Regulation of ion channel expression and gating by cellular redox state is a widely accepted mechanism; however, it remains a matter of debate whether an increase or a decrease in reactive oxygen species (ROS) occurs under hypoxic conditions. Ion channel redox regulation has been described in detail for some ion channels, such as Kv channels or TRPC6. However, in general information on ion channel redox regulation remains scant. Critical issues and future directions: In addition to the debate of increased vs. decreased ROS production during hypoxia, we aim here to describe and decipher why different oxidants, under different conditions can cause both, activation and inhibition of channel activity. While the upstream pathways affecting channel gating are often well described, we need a better understanding of redox protein modifications in order to be able to determine the complexity of ion channel redox regulation. Against this background we summarize the current knowledge on hypoxia-induced ROS-mediated ion channel signaling in the pulmonary circulation.
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