Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel.
TREK-1 is a member of the novel structural class of K(+) channels with four transmembrane segments and two pore domains in tandem (1,2). TREK-1 is opened by membrane stretch and arachidonic acid. It is also an important target for volatile anesthetics (2,3). Here we show that internal acidification opens TREK-1. Indeed, lowering pH(i) shifts the pressure-activation relationship toward positive values and leads to channel opening at atmospheric pressure. The pH(i)-sensitive region in the carboxyl terminus of TREK-1 is the same that is critically involved in mechano-gating as well as arachidonic acid activation. A convergence, which is dependent on the carboxyl terminus, occurs between mechanical, fatty acids and acidic stimuli. Intracellular acidosis, which occurs during brain and heart ischemia, will induce TREK-1 opening with subsequent K(+) efflux and hyperpolarization.
Maingret
F
F
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Patel
A J
AJ
Lesage
F
F
Lazdunski
M
M
Honoré
E
E
D000143:Acids / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D051379:Mice; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D013314:Stress, Mechanical; D014162:Transfection
D000143:Acids; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1