Effects of hyperthermia on the membrane potential and Na+ transport of V79 fibroblasts.
The effects of hyperthermia (41-43 degrees C) on the membrane potential (calculated from the transmembrane distribution of [3H]tetraphenylphosphonium) and Na+ transport of Chinese hamster V79 fibroblasts were studied. At 41 degrees C, hyperthermia induced a membrane hyperpolarization of log phase cells (5 to 26 mV) that was reversible upon returning to 37 degrees C. The hyperpolarization was inhibited 50% by 1 mM ouabain or 0.25 mM amiloride, an inhibitor of Na+:H+ exchange. Shifting temperature to 41 degrees C increased ouabain-sensitive Rb+ uptake indicating activation of the electrogenic Na+ pump. At 43 degrees C for 60 min, the membrane potential of log phase cells depolarized (20-35 mV). Parallel studies demonstrated enhanced Na+ uptake at 41 degrees C only in the presence of ouabain. At 43 degrees C, Na+ uptake was increased relative to controls with or without ouabain present. At both 41 and 43 degrees C, 0.25 mM amiloride inhibited heat-stimulated Na+ uptake. Na+ efflux was enhanced at 41 degrees C in a process inhibited by ouabain. Thus, one consequence of heat treatment at 41 degrees C is activation of Na+:H+ exchange with the resultant increase in cytosolic [Na+] activating the electrogenic Na+ pump. At temperatures greater than or equal to 43 degrees C, the Na+ pump is inhibited.
Mikkelsen
R B
RB
Department of Radiation Oncology, New England Medical Center, Boston, Massachusetts 02111.
Asher
C R
CR
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D006358:Hot Temperature; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D009861:Onium Compounds; D009943:Organophosphorus Compounds; D010042:Ouabain; D000968:Antimycin A; D000584:Amiloride; D012964:Sodium; D012413:Rubidium; C013289:tetraphenylphosphonium