Effects of hyperthermia on intracellular chloride.

Hyperthermia induces transient changes in [Na+]i and [K+]i in mammalian cells. Since Cl- flux is coupled with Na+ and K+ in several processes, including cell volume control, we have measured the effects of heat on [Cl-]i using the chloride indicator, MQAE, with flow cytometry. The mean basal level of [Cl-]i in Chinese hamster ovary cells was 12 mM. Cells heated at 42.0 degrees or 45.0 degrees C for 30 min had about a 2.5-fold increase in [Cl-]i above unheated control values when measured immediately after heating. There was about a 3-fold decrease in [Na+]i under the same conditions, as measured by Sodium Green. The magnitude of the increase in [Cl-]i depended upon time and temperature. The [Cl-]i recovered in a time-dependent fashion to control values by 30 min after heating. When cells were heated at 45.0 degrees C for 30 min in the presence of 1.5 mM furosemide, the heat-induced [Cl-]i increase was completely blocked. Since furosemide inhibits the Na+/K+/2Cl- cotransporter, Cl- channels, and even Cl-HCO3 exchange, these ion transporters may be involved in the heat-induced increase in [Cl-]i.