TRAAK Is a Mammalian Neuronal Mechano-gated K+Channel

Abstract

The novel structural class of mammalian channels with four transmembrane segments and two pore regions comprise background K ؉ channels (TWIK-1, TREK-1, TRAAK, TASK, and TASK-2) with unique physiological functions (1-6). Unlike its counterparts, TRAAK is only expressed in neuronal tissues, including brain, spinal cord, and retina (1). This report shows that TRAAK, which was known to be activated by arachidonic acid (3), is also opened by membrane stretch. Mechanical activation of TRAAK is induced by a convex curvature of the plasma membrane and can be mimicked by the amphipathic membrane crenator trinitrophenol. Cytoskeletal elements are negative tonic regulators of TRAAK. Membrane depolarization and membrane crenation synergize with stretch-induced channel opening. Finally, TRAAK is reversibly blocked by micromolar concentrations of gadolinium, a well known blocker of stretch-activated channels. Mechanical activation of TRAAK in the central nervous system may play an important role during growth cone motility and neurite elongation.

Swelling-activated and arachidonic acid-induced currents are TREK-1 in rat bladder smooth muscle cells

“…This is the first report showing that swelling activates an outwardly rectifying K + current in rat bladder myocytes. This channel was activated by cell swelling caused by an external hypo -osmotic condition, and was inhibited by gadolinium (Gd 3+ ), which inhibits stretch activated nonselective cation current (Yang & Sachs 1989) and stretch activated K + channels (Maingret et al 1999. Raising the K + concentration in the hypotonic bath solution without changing osmolarity shifted the reversal potential of the SAC current in a positive direction, consistent with K + permeability of the SAC.…”

“…The stretch -activated K + channels reported to date are TREK -1, TREK -2 and TRAAK, which are a mechanosensitive subgroup of the four transmembrane two pore domain K + channel family and are expressed in many regions in the brain as well as in certain peripheral tissues, such as ovary and small intestine (Medhurst et al 2001). They behave as a background K + current and are modulated not only by mechanical stretch but also by unsaturated free fatty acids such as arachidonic acid, and are inhibited by Gd 3+ (Maingret et al 1999Ferroni et al 2003). In the present study, arachidonic acid activated a significant outwardly rectifying K + current in rat bladder cells which was inhibited by Gd 3+ .…”

“…1998 ; Maingret et al 1999 ;Bang et al 2000) and also activated by arachidonic acid (AA) Patel et al 1998 ;Bang et al 2000). Therefore, we examined the effect of AA on the rat bladder smooth muscle cells.…”

“…They are non -selective cation channels (Popp et al 1992 ;Kim 1993), Ca 2+ channels (Lansman et al 1987), Cl --selective anion channels (Tseng 1992 ;Okada 1997), ATP -sensitive K + channels (Van Wagoner & Russo 1992), K + -selective channels (Guharay & Sachs 1984 ;Sigurdson et al 1987), and two -pore domain K + channels called TREK and TRAAK family (Patel et al 1998 ;Bang et al 1999 ;Maingret et al 1999).…”

New paradigms in the mechanisms and management of glaucoma

“…56 In order to recognize that axonal shape is being altered by external forces, pressure sensitive channels (TRAAK channels) may be the operative pathway. 57 RGC axons might be made less sensitive to compression through manipulation of TRAAK channel sensitivity. A molecule that deserves study, the motor protein that carries messenger proteins on their receptors, is dynein, a huge complex riding along the axonal microtubules.…”