AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 2 203-L208, Copyright © 1995 by American Physiological Society
Inhibition of glycolysis by 2-DG increases [Ca2+]i in pulmonary arterial smooth muscle cells
R. T. Bright, C. G. Salvaterra, L. J. Rubin and X. J. Yuan
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Inhibition of glycolysis depolarizes single pulmonary arterial smooth
muscle cells (PASMC) and potentiates hypoxic pulmonary vasoconstriction
(HPV) in isolated perfused rat lungs. Whether glycolytic inhibition causes
an increase in the intracellular Ca2+ concentration ([Ca2+]i) in PASMC was
determined in this study. [Ca2+]i was measured in primary cultured rat
PASMC using the Ca2+ -sensitive fluorescent indicator, fura 2, and
quantitative fluorescence microscopy. Extracellular application of the
glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), significantly and
reversibly increased [Ca2+]i in PASMC. Removal of extracellular Ca2+ and
application of the Ca2+ channel blocker, verapamil (10 microM), attenuated,
but did not eliminate, the 2-DG-induced rise in [Ca2+]i. In the absence of
extracellular Ca2+, however, depletion of inositol triphosphate-sensitive
intracellular Ca2+ stores by 10 microM cyclopiazonic acid (CPA) completely
abolished the 2-DG-induced increase in [Ca2+]i. The data suggest that
2-DG-induced increases in [Ca2+]i result from both Ca2+ influx through the
verapamil-sensitive voltage-gated Ca2+ channels and Ca2+ release from the
CPA-sensitive intracellular Ca2+ stores.
