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 Ba(2+)) but completely inhibited by tetracaine (200 microM), an inhibitor of TREK channels. The heat-induced hyperpolarization was mimicked by 10 microM 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.
Zhang
Hengtao
H
Jean and George Brumley, Jr. Neonatal-Perinatal Research Institute, Department of Pediatrics/Division of Neonatology, Duke University Medical Center, Box 3179, Durham, NC 27710, USA. zht@duke.edu
Shepherd
Neal
N
Creazzo
Tony L
TL
D000818:Animals; D002642:Chick Embryo; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D013748:Tetracaine / Q000494:pharmacology
D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D013748:Tetracaine; D011188:Potassium