Modulation of non-inactivating K+ channels in mouse TREK-1 transfected HEK cells by hallothane and isoflurane

Abstract

Inhibition of neuronal activity via membrane hyperpolarization not only caused by influx of chloride ions through GABAA and glycine receptor channels but also efflux of cations through channels that are specified for K+. Seven years ago, a new family of two pore tandem potassium channels has been identified. Members of this family presents structural features that suggests dimeric arrangement with each subunit comprising four transmembrane (TM) segments and two pore-forming regions (2 PK). Recently, it is reported that KCNK3 (TASK-1) was present in rat cerebellar granule neurons and also volatile anesthetics modulates KCNK activity (TREK-1, TASK-1 and TASK-2) in transfected COS-7 and HEK-293 cells. Except GABAA and glycine channels, newly discovered tandem pore potassium channels are also activated by volatile anesthetics.1, 2) KCNK2 (TREK-1) is a member of novel class of K+ channels with four transmembrane segments and two pore domains in tandem.3) Mouse KCNK2, like the other channels in this family, has been shown to control resting membrane potential. Distribution pattern of mouse KCNK2 was found to be highly expressed in lung in addition to brain, and also showed expression in kidney, heart and skeletal muscle. This channel had low levels of expression in the CNS area, with highest signals being observed in the olfactory bulb, the hippocampal formation and cerebellum. Within the mouse brain the strongest signals arose from the olfactory bulb, hippocampal formation and cerebellum. TREK-1 is mechanosensitive and its gating is altered considerably by agents that affect the structure of the cell membrane. Most interestingly TREK-1 channels can be modulated by the volatile anesthetics. .4) The goal of this study is to test the effect of clinically relevant concentrations of volatile anesthetics on the currents through the K+ channels in the mouse KCNK2 transfected HEK cells.