Dual conductance mode of the TREK-1 channel: A hidden track to mechanoelectric regulation in the heart?

Abstract

See article by Li et al. [12] (pages 86–97) in this issue. Two-pore-domain K+ channels (K2P channels) form a novel class of K+ channels identified in various types of cells. K2P channels display constitutive activity at around the resting membrane potential and are sensitively regulated by various physical and chemical factors [1,2]. Among the members of K2P channels, TREK and TRAAK families respond to the widest variety of stimuli including pH, temperature, unsaturated fatty acids, phospholipids, volatile anesthetics, and membrane stretch [1,2]. The mechanical gating of TREK seems to arise from the direct interaction between the membrane phospholipid and the sensor domain of the channel without involvement of the actin cytoskeleton [3]. The heart undergoes incessant cyclic stretch and sudden changes in volume loading. Such mechanical stress provokes electrical responses termed “mechanoelectric feedback” [4]. To elucidate the mechanism, the role of stretch-activated signal transduction and mechanosensitive nonselective cation channels (NSCMS) have been persistently investigated [5–7]. Besides the more widely recognized NSCMS at the level of whole-cell or tissue experiments, the stretch of local membranes via the patch pipette technique showed mechanosensitive K+ channels in rat atrial myocytes that are also activated by intracellular acidification and arachidonic acids [8,9]. After the … *Corresponding author. Tel.: +82 2 740 8224; fax: +82 2 763 9667. Email address: earmye{at}snu.ac.kr