Inhibition of glycolysis by 2-DG increases [Ca2+]i in pulmonary arterial smooth muscle cells.
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.
Bright
R T
RT
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Salvaterra
C G
CG
Rubin
L J
LJ
Yuan
X J
XJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D007211:Indoles; D003847:Deoxyglucose; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid