These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells.
    Author: Yuan XJ, Tod ML, Rubin LJ, Blaustein MP.
    Journal: Am J Physiol; 1994 Jul; 267(1 Pt 1):L52-63. PubMed ID: 8048542.
    Abstract:
    Hypoxia-induced pulmonary vasoconstriction (HPV) is triggered by a rise in cytosolic Ca2+ concentration ([Ca2+]i) that is partially controlled by voltage-gated Ca2+ channels. Hypoxia inhibits voltage-gated K+ (KV) channels in pulmonary artery (PA) myocytes. This depolarizes the cells, opens voltage-gated Ca2+ channels, thereby increases [Ca2+]i, and initiates HPV. In intact animals and isolated perfused lungs, metabolic inhibitors and reducing agents augment HPV. We compared the effects of hypoxia with the glycolysis inhibitor, 2-deoxy-D-glucose (2-DOG), and the reducing agent, reduced glutathione (GSH), on voltage-gated steady-state K+ currents (IK,ss) and membrane potential (Em) in cultured rat pulmonary and mesenteric arterial (MA) smooth muscle cells. Bath application of 10 mM 2-DOG (glucose-free) or 5-10 mM GSH reversibly reduced IK,ss by 25-35% in PA myocytes, with 5 mM ATP present in the pipette solution. Neither hypoxia nor 2-DOG significantly affected IK,ss in MA myocytes, but GSH did reduce IK,ss in these cells. Furthermore, hypoxia, 2-DOG, and GSH depolarized PA cells in the absence as well as in the presence of external Ca2+. Hypoxia, 2-DOG, and GSH also evoked action potentials on the top of the steady depolarization in 36-50% of PA myocytes but not in any MA myocytes; removal of external Ca2+ abolished the action potentials without affecting the steady depolarization. These effects were comparable to those produced by 4-aminopyridine (5-10 mM), a blocker of KV channels. This implies that the action potentials are attributable to Ca2+ influx through voltage-gated Ca2+ channels opened by the steady depolarization due to KV channel inhibition. In the presence of 2-DOG or GSH, hypoxia had no further effect on IK,ss or Em in PA cells; this implies that hypoxia, 2-DOG, and GSH all block the same K+ channels. The data suggest that 1) the hypoxia-induced decrease of IK,ss and the resultant depolarization in PA myocytes may be related to a local decrease of intracellular ATP level and/or a change in redox status of the membrane or cytosol and 2) extracellular Ca(2+)-dependent action potentials may be responsible for at least part of the increase in [Ca2+]i during HPV. Similarities between the effects of hypoxia, 2-DOG, and GSH on IK,ss and Em in PA myocytes, along with the dissimilar responses of PA and MA myocytes, suggest that a common mechanism may underlie the responses of PA cells to these treatments.
    [Abstract] [Full Text] [Related] [New Search]