Effects of hyperthermia on the membrane potential and Na+ transport of V79 fibroblasts

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Abstract
The effects of hyperthermia (41–43°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°C, hyperthermia induced a membrane hyperpolarization of log phase cells (5 to 26 mV) that was reversible upon returning to 37°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°C increased ouabain-sensitive Rb+ uptake indicating activation of the electrogenic Na+ pump. At 43°C for 60 min, the membrane potential of log phase cells depolarized (20–35 mV). Parallel studies demonstrated enhanced Na+ uptake at 41°C only in the presence of ouabain. At 43°C, Na+ uptake was increased relative to controls with or without ouabain present. At both 41 and 43°C, 0.25 mM amiloride inhibited heat-stimulated Na+ uptake. Na+ efflux was enhanced at 41°C in a process inhibited by ouabain. Thus, one consequence of heat treatment at 41°C is activation of Na+:H+ exchange with the resultant increase in cytosolic [Na+] activating the electrogenic Na+ pump. At temperatures ≥43°C, the Na+ pump is inhibited.