A TREK-1-like potassium channel in atrial cells inhibited by beta-adrenergic stimulation and activated by volatile anesthetics

Many members of the two-pore-domain potassium (K+) channel family have been detected in the mammalian heart but the endogenous correlates of these cha nnels still have to be identified. We investigated whether I-KAA, a backgro und K+ 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 config uration of the patch-clamp technique, we found that I-KAA, like TREK-1, was outwardly rectifying in physiological K+ conditions, with a conductance of 41 pS at +50 mV. Like TREK-1, I-KAA was reversibly activated by clinical c oncentrations of volatile anesthetics (in mmol/L, chloroform 0.18, halothan e 0.11, and isoflurane 0.69). In cell-attached experiments, I-KAA was inhib ited by chlorophenylthio-cAMP (500 mu mol/L) and also by stimulation of bet a -adrenergic receptors with isoproterenol (1 mu mol/L). In addition, TREK- 1 mRNAs were detected in all cardiac tissues, and the TREK-1 protein was im munolocalized in isolated atrial myocytes. Such a background potassium chan nel might contribute to the positive inotropic effects produced by beta -ad renergic stimulation of the heart. It might also be involved in the regulat ion of the atrial natriuretic peptide secretion.