Calcium, mitochondria and oxygen sensing in the pulmonary circulation

TY - JOUR

T1 - Calcium, mitochondria and oxygen sensing in the pulmonary circulation

AU - Ward, J P T

AU - Snetkov, V A

AU - Aaronson, P I

PY - 2004/9

Y1 - 2004/9

N2 - A key event in hypoxic pulmonary vasoconstriction (HPV) is the elevation in smooth muscle intracellular Ca2+ concentration. However, there is controversy concerning the source of this Ca2+, the signal transduction pathways involved, and the identity of the oxygen sensor. Although there is wide support for the hypothesis that hypoxia elicits depolarisation via inhibition of K+ channels, and thus promotes Ca2+ entry through L-type channels, a significant number of studies are inconsistent with this mechanism being either the sole or even major means by which Ca2+ is elevated during HPV. There is strong evidence that intracellular Ca2+ stores play a critical role, and voltage-independent Ca2+ entry (CCE) have also been implicated. There is renewed interest in the role of mitochondria entry mechanisms including capacitative Ca2+ in HPV, both in terms of modulators of Ca2+ homeostasis per se and as oxygen sensors. There is however considerable uncertainty concerning the mechanisms involved in the latter, with proposals for changes in redox couples and both an increase and decrease in mitochondrial production of reactive oxygen species (ROS). In this article we review the evidence for and against involvement of such mechanisms in HPV, and in pulmonary artery during hypoxia in which the mitochondria play a central role. propose a model for the regulation of intracellular [Ca2+] (C) 2004 Elsevier Ltd. All rights reserved.

AB - A key event in hypoxic pulmonary vasoconstriction (HPV) is the elevation in smooth muscle intracellular Ca2+ concentration. However, there is controversy concerning the source of this Ca2+, the signal transduction pathways involved, and the identity of the oxygen sensor. Although there is wide support for the hypothesis that hypoxia elicits depolarisation via inhibition of K+ channels, and thus promotes Ca2+ entry through L-type channels, a significant number of studies are inconsistent with this mechanism being either the sole or even major means by which Ca2+ is elevated during HPV. There is strong evidence that intracellular Ca2+ stores play a critical role, and voltage-independent Ca2+ entry (CCE) have also been implicated. There is renewed interest in the role of mitochondria entry mechanisms including capacitative Ca2+ in HPV, both in terms of modulators of Ca2+ homeostasis per se and as oxygen sensors. There is however considerable uncertainty concerning the mechanisms involved in the latter, with proposals for changes in redox couples and both an increase and decrease in mitochondrial production of reactive oxygen species (ROS). In this article we review the evidence for and against involvement of such mechanisms in HPV, and in pulmonary artery during hypoxia in which the mitochondria play a central role. propose a model for the regulation of intracellular [Ca2+] (C) 2004 Elsevier Ltd. All rights reserved.

UR - http://www.scopus.com/inward/record.url?scp=3342938491&partnerID=8YFLogxK

U2 - 10.1016/j.ceca.2004.02.017

DO - 10.1016/j.ceca.2004.02.017

M3 - Article

VL - 36

SP - 209

EP - 220

JO - Cell Calcium

JF - Cell Calcium

IS - 3-4

ER -