Temperature-sensitive TREK currents contribute to setting the resting membrane potential in embryonic atrial myocytes

TREK channels belong to the superfamily of two-pore-domain K+ channels and are activated by membrane stretch, arachidonic acid, volatile anaesthetics and heat. TREK-1 is highly expressed in the atrium of the adult heart. In this study, we investigated the role of TREK-1 and TREK-2 channels in regulating the resting membrane potential (RMP) of isolated chicken embryonic cardiac myocytes. At room temperature, the average RMP of embryonic day (ED) 11 atrial myocytes was -22 +/- 2 mV. Raising the temperature to 35 degrees C hyperpolarized the membrane to -69 +/- 2 mV and activated a large outwardly rectifying K+ current that was relatively insensitive to conventional K+ channel inhibitors (TEA, 4-AP and Ba2+) but completely inhibited by tetracaine (200 mu M), an inhibitor of TREK channels. The heat-induced hyperpolarization was mimicked by 10 mu M arachidonic acid, an agonist of TREK channels. There was little or no inwardly rectifying K+ current (I-K1) in the ED11 atrial cells. In marked contrast, ED11 ventricular myocytes exhibited a normal RMP (-86.1 +/- 3.4 mV) and substantial I-K1, but no temperature- or tetracaine-sensitive K+ currents. Both RT-PCR and real-time PCR further demonstrated that TREK-1 and TREK-2 are highly and almost equally expressed in ED11 atrium but much less expressed in ED11 ventricle. In addition, immunofluorescence demonstrated TREK-1 protein in the membrane of atrial myocytes. These data indicate the presence and function of TREK-1 and TREK-2 in the embryonic atrium. Moreover, we demonstrate that TREK-like currents have an essential role in determining membrane potential in embryonic atrial myocytes, where I-K1 is absent.