Activation of potassium channels: relationship to the heat shock response.
We examined the possibility that whole cell currents are involved and possibly trigger the response of mammalian cells to heat shock. Heat-sensitive cells from a radiation-induced fibrosarcoma (RIF-1) and heat-resistant variants (TR-4, TR-5) were heated at 45 degrees C for 3-30 min. We observed induction of voltage-dependent currents after heating in the heat-resistant cells. These currents decayed to nonmeasurable levels over a period of 6 h. In RIF-1 cells, however, voltage-dependent currents were detectable during heating only; these currents then decayed rapidly. Tetraethylammonium (TEA) cations blocked the currents; changing the concentration of extracellular K+ modified the current-voltage (I-V) relationship. These currents, therefore, resulted from the activation of voltage-dependent K+ channels. Addition of TEA during heating sensitized TR-4 cells to heat but had no effect on the heat response of the RIF-1 cells. Continuous exposure of the RIF-1 cells to 2% (vol/vol) dimethyl sulfoxide (DMSO) for 7 days induced the expression of additional functional, voltage-dependent K+ channels; these gave rise to currents that were measurable after heating. In parallel, these cells became heat resistant. Addition of TEA to DMSO-treated cells blocked channels and returned the heat response almost to the pre-DMSO levels. Our data show a correlation between heat resistance and expression of K+ channels. Because resistance to heat very likely relates to the heat shock response, our data suggest that activation of channels may be a very early event in initiation of the heat shock response.
Saad
A H
AH
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305-5468.
Hahn
G M
GM
D000818:Animals; D002470:Cell Survival; D004553:Electric Conductivity; D006358:Hot Temperature; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008322:Mammals; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D011188:Potassium