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J Physiol Volume 564, Number 1, 103-116, April 1, 2005 DOI: 10.1113/jphysiol.2004.081059
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Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK

Dawon Kang1, Changyong Choe2 and Donghee Kim3

1 Department of Physiology, Gyeongsang National University School of Medicine, Jinju 660-751, Korea
2 National Livestock Research Institute, Rural Development Administration, Namwon 590-832, Korea
3 Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA

TREK-1, TREK-2 and TRAAK are members of the two-pore domain K+ (K2P) 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 K2P 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.

(Received 10 December 2004; accepted after revision 24 January 2005; first published online 27 January 2005)
Corresponding author D. Kim: Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. Email: donghee.kim{at}rosalindfranklin.edu




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