Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells

X. J. Yuan, M. L. Tod, L. J. Rubin, M. P. Blaustein

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80 Scopus citations


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+ (K(V)) 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 (I(K,ss)) and membrane potential (E(m)) 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 I(K,ss) by 25-35% in PA myocytes, with 5mM ATP present in the pipette solution. Neither hypoxia nor 2-DOG significantly affected I(K,ss) in MA myocytes, but GSH did reduce I(K,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 K(V) channels. This implies that the action potentials are attributable to Ca2+ influx through voltage-gated Ca2+ channels opened by the steady depolarization due to K(V) channel inhibition. In the presence of 2-DOG or GSH, hypoxia had no further effect on I(K,ss) or E(m) 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 I(K,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 Ca2+-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 I(K,ss) and E(m) 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.

Original languageEnglish (US)
Pages (from-to)L52-L63
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 11-1
StatePublished - 1994
Externally publishedYes


  • glycolysis
  • pulmonary and mesenteric arterial smooth muscle cells
  • redox status
  • voltage-gated potassium channels

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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