Thermosensitivity of the two‐pore domain K+ channels TREK‐2 and TRAAK

Abstract

TREK‐1, TREK‐2 and TRAAK are members of the two‐pore domain K+ (K 2P) channel family and are activated by membrane stretch and free fatty acids. TREK‐1 has been shown to be sensitive to temperature in expression systems. We studied the temperature‐sensitivity of TREK‐2 and TRAAK in COS‐7 cells and in neuronal cells. In transfected COS‐7 cells, TREK‐2 and TRAAK whole‐cell currents increased ∼20‐fold as the bath temperature was raised from 24°C to 42°C. Similarly, in cell‐attached patches of COS‐7 cells, channel activity was very low, but increased progressively as the bath temperature was raised from 24°C to 42°C. The thresholds for activation of TREK‐2 and TRAAK were ∼25°C and ∼31°C, respectively. Other K 2P channels such as TASK‐3 and TRESK‐2 were not significantly affected by an increase in temperature from 24°C to 37°C. When the C‐terminus of TREK‐2 was replaced with that of TASK‐3, its sensitivity to free fatty acids and protons was abolished, but the mutant could still be activated by heat. At 37°C, TREK‐1, TREK‐2 and TRAAK were sensitive to arachidonic acid, pH and membrane stretch in both cell‐attached and inside‐out patches. In cerebellar granule and dorsal root ganglion neurones, TREK‐1, TREK‐2 and TRAAK were generally inactive in the cell‐attached state at 24°C, but became very active at 37°C. In cell‐attached patches of ventricular myocytes, TREK‐1 was also normally closed at 24°C, but was active at 37°C. These results show that TREK‐2 and TRAAK are also temperature‐sensitive channels, are active at physiological body temperature, and therefore would contribute to the background K+ conductance and regulate cell excitability in response to various physical and chemical stimuli.