Cytoplasmic phosphates in Na(+)-K+ balance in KCN-poisoned rat heart: a 87Rb-, 23Na-, and 31P-NMR study.
The effect on intracellular Na+ ([Na+]i) and Rb+ fluxes if reduced [ATP]/ [ADP] and increased Pi has been investigated by 1 mM potassium cyanide (KCN) or KCl (control) infusion (24 min) in Langendorff perfused rat hearts. 87Rb, 23Na, or 31P nuclear magnetic resonance (NMR) spectra were acquired to measure intracellular Rb+ (a congener for K+, 20% substitution), Na+, and phosphates. KCN infusion (14-24 min) caused decreases in phosphocreatine (34 +/- 12% of initial), ATP (64 +/- 17), and Rb content (71 +/- 7) and increases in Pi (273 +/- 65) and [Na+]i (210 +/- 52). Dimethylamiloride (10 microM) did not change the rate of Na+ accumulation. The rate constant of unidirectional Rb+ efflux (min-1) increased during KCN treatment by 70% (0.061 +/- 0.006 vs. 0.036 +/- 0.004, P = 0.0001). KCN-stimulated Rb+ efflux was inhibited by glibenclamide (Glib, 10 microM. 0.042 +/- 0.009, P = 0.0001 vs. KCN) and alpha-cyano-4-hydroxycinnamate (0.5 mM, 0.047 +/- 0.008, P < 0.002 vs. KCN). KCN moderately decreased the Rb+ influx rate (to 82 +/- 17%, P = 0.01), which was depressed more significantly in the presence of Glib (47 +/- 17%, P = 0.03). We suggest that inhibition of Na(+)-K(+)-adenosinetriphosphatase (ATPase) by Pi is responsible for intracellular Na+ accumulation, whereas K+ loss is associated with both activation of ATP-sensitive K+ channels and the K(+)-lactate-cotransporter and inhibition of Na(+)-K(+)-ATPase.
Kupriyanov
V V
VV
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba, Canada.
Yang
L
L
Deslauriers
R
R
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus; D011188:Potassium / Q000378:metabolism*; D011190:Potassium Cyanide / Q000506:poisoning*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism*
D010710:Phosphates; D012414:Rubidium Radioisotopes; D010758:Phosphorus; D012964:Sodium; D012413:Rubidium; D011190:Potassium Cyanide; D011188:Potassium