Abstract-Many members of the two-pore-domain potassium (K ϩ ) channel family have been detected in the mammalian heart but the endogenous correlates of these channels still have to be identified. We investigated whether I KAA , a background K ϩ current activated by negative pressure (stretch) and by arachidonic acid (AA) and sensitive to intracellular acidification, could be the native correlate of TREK-1 in adult rat atrial cells. Using the inside-out configuration of the patch-clamp technique, we found that I KAA , like TREK-1, was outwardly rectifying in physiological K ϩ conditions, with a conductance of 41 pS at ϩ50 mV. Like TREK-1, I KAA was reversibly activated by clinical concentrations of volatile anesthetics (in mmol/L, chloroform 0.18, halothane 0.11, and isoflurane 0.69). In cell-attached experiments, I KAA was inhibited by chlorophenylthio-cAMP (500 mol/L) and also by stimulation of -adrenergic receptors with isoproterenol (1 mol/L). In addition, TREK-1 mRNAs were detected in all cardiac tissues, and the TREK-1 protein was immunolocalized in isolated atrial myocytes. Such a background potassium channel might contribute to the positive inotropic effects produced by -adrenergic stimulation of the heart. It might also be involved in the regulation of the atrial natriuretic peptide secretion. Key Words: potassium channels Ⅲ volatile anesthetics Ⅲ -adrenergic receptor Ⅲ heart cells C ardiac potassium (K ϩ ) channels have extensively been studied for years. In the working atrial and ventricular myocytes, they belong to the following two major families: (1) the voltage-dependent channels (I to , I Kr , I Ks , etc), which are involved in the different repolarization phases of the cardiac action potential (AP), and (2) the background K ϩ channels, which stabilize the resting membrane potential at a hyperpolarized level and regulate AP duration in physiological conditions (I K1 ), during sympathetic stimulation of the heart (I KACh ), or during pathological events such as ischemia (I KATP , etc) (for a review, see Carmeliet 1 ).During the last decade, a large number of K ϩ channel ␣ subunits were cloned and further characterized in expression systems such as Xenopus oocytes and mammalian cell lines (COS, HEK, etc). Some of these cloned channels were proposed as molecular substrates for the endogenous cardiac K ϩ currents on the basis of their biophysical and pharmacological properties. For instance, Kv4.2 is suggested to be a molecular correlate of I to , whereas HERG and KvLQT1/Isk correspond to I Kr and I Ks , respectively. 2-6 IRK1 (Kir2.1) generates a current similar to that of I K1 , whereas GIRK1 (Kir3.1) forms a complex with GIRK4 (Kir3.4) to reproduce I KACh . 7,8 Kir6.2 coassembles with the sulfonylurea receptor SUR2A to reconstitute the cardiac K ATP channel. 9,10 However, not all cloned K ϩ channel ␣ subunits shown to be expressed in the heart have been associated with an endogenous channel. This is particularly the case for the expanding family of mammalian two-pore-domain potassium (K 2P ) cha...