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Abstract: Extracellular acidic pH activated chloride channels (ICl,acid) have been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to evaluate the expression of ICl,acid in RAW264.7 monocytic-macrophage and human peripheral monocytes and to investigate the effect of simvastatin on ICl,acid. In two kinds of cells, the activation and deactivation of the current rapidly and repeatedly followed the change of the extracellular solution to pH=4.3. Compared with the outward current (pA/pF) activated at pH 4.3, the currents inhibited by simvastatin at concentrations of 0.1 μM were all decreased a little, however the currents at concentrations of 1 μM and 10 μM simvastatin were decreased significantly. The IC50 for simvastatin inhibiting ICl,acid of RAW264.7 was 13.77 μM. In summary, we report for the first time that simvastatin inhibits the ICl,acid of RAW264.7 monocytic-macrophage and human peripheral monocytes in a concentration-dependent manner. [Copyright &y& Elsevier]

Abstract: Extracellular acidic pH-activated chloride channel I Cl, acid, has been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to characterize I Cl,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 I Cl,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 (100μM). 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 Cl,acid would play a role in regulation of EC function under these pathological conditions. [Copyright &y& Elsevier]