Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Weir, EK; Olschewski, A.
Role of ion channels in acute and chronic responses of the pulmonary vasculature to hypoxia.
CARDIOVASC RES. 2006; 71(4): 630-641.
Doi: 10.1016/j.cardiores.2006.04.014
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- Führende Autor*innen der Med Uni Graz
- Olschewski Andrea
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- Abstract:
- Localized alveolar hypoxia causes constriction of the small resistance pulmonary arteries, thus diverting the desaturated, mixed-venous blood to better ventilated areas of the lung. Although modulated by endothelial vasoactive substances, the constrictor response to hypoxia is intrinsic to the smooth muscle cell. Ion channels are important elements in two of the three components of the response. Hypoxia inhibits several potassium channels (voltage-gated and TASK), leading to membrane depolarization and calcium entry through L-type channels. It also causes release of calcium from the sarcoplasmic reticulum, with consequent repletion through store-operated calcium channels. Finally, the effect of the rise in cytosolic calcium is amplified by enhanced calcium sensitivity of the actin/myosin interaction, achieved by the hypoxia-induced increase in Rho-kinase activity. The change in oxygen tension that stimulates these three "executive" components is signaled by a change in the redox status of the smooth muscle cell and probably by downstream changes in G-proteins. Ion channels also play a critical role in the vascular remodeling that results in chronic hypoxic pulmonary hypertension, seen when all the pulmonary vascular bed is hypoxic, at high altitude and in patients with chronic lung diseases. The same inhibition of potassium channels and influx of calcium results in high cytosolic levels of potassium and calcium. These, respectively, lead to inhibition of apoptosis and an increase in cellular proliferation. A better understanding of the pathophysiology of hypoxic pulmonary vasoconstriction and vascular remodeling will enable the design of better treatments for hypoxic and other forms of pulmonary hypertension.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptation, Physiological -
- Animals -
- Anoxia - metabolism
- Calcium - metabolism
- Humans - metabolism
- Hypertension, Pulmonary - metabolism
- Ion Channel Gating - metabolism
- Ion Channels - metabolism
- Pulmonary Artery - physiology
- Pulmonary Circulation - physiology
- Pulmonary Edema - metabolism
- Vasoconstriction - physiology
- Find related publications in this database (Keywords)
- hypoxic pulmonary vasoconstriction
- K+ channels
- Ca2+ channels
- cytosolic Ca2+
- hypoxic pulmonary hypertension
- vascular remodeling
- pulmonary arterial smooth muscle cells
- oxygen-sensing