Ion channels in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a hemodynamic abnormality that ultimately results in mortality due to right heart failure. Although the clinical manifestations of primary and secondary PAH are diverse, medial hypertrophy and arterial vasoconstriction are key components in the vascular remodeling leading to PAH. Abnormalities in the homeostasis of intracellular Ca(2+), transmembrane flux of ions, and membrane potential may play significant roles in the processes leading to pulmonary vascular remodeling. Decreased activity of K(+) channels causes membrane depolarization, leading to Ca(2+) influx. The elevated cytoplasmic Ca(2+) is a major trigger for pulmonary vasoconstriction and an important stimulus for vascular smooth muscle proliferation. Dysfunctional K(+) channels have also been linked to inhibition of apoptosis and contribute further to the medial hypertrophy. This review focuses on the relative role of K(+) and Ca(2+) ions and channels in human pulmonary artery smooth muscle cells in the development of PAH.
Mandegar
Mehran
M
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, USA.
Remillard
Carmelle V
CV
Yuan
Jason X-J
JX
D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D006984:Hypertrophy / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D015222:Sodium Channels / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction
D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels; D002118:Calcium