Extracellular acidic pH-activated chloride channel I-C1,I- (acid), has been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to characterize I-C1,I-acid in human umbilical vein endothelial cells(HUVECs). The activation and deactivation of the current rapidly and repeatedly follows the change of the extracellular solution at pH 4.3, with the threshold pH 5.3. In addition, at very positive potentials, the current displays a time-dependent facilitation. pH-response relationship for IC1,acid revealed that EC50 is pH 4.764 with a threshold pH value of pH 5.3 and nH of 14.545. The current can be blocked by the Cl- channel inhibitor DIDS (100 mu M). In summary, for the first time we report the presence of proton-activated, outwardly rectifying chloride channel in HUVECs. Because an acidic environment can develop in local myocardium under pathological conditions such as myocardial ischemia, I-C1,I-acid would play a role in regulation of EC function under these pathological conditions. (C) 2008 Elsevier Inc. All rights reserved.