title: Tricarbonyldichlororuthenium (II) dimer (CORM2) activates non-selective cation current in human endothelial cells independently of carbon monoxide releasing.
abstract: Tricarbonyldichlororuthenium (II) dimer (CORM2) has been developed as carbon monoxide (CO) donor. We found that CORM2 activated a type of specific current which was distinct from the big-conductance Ca(2+)-activated K(+) current activated by CO in human umbilical vein endothelial cells (HUVECs). So the aim of the present study was to characterize the CORM2-induced current and to access the relation with CO releasing. CORM2 (100 microM) activated a kind of bi-directional current in HUVECs when the ramp protocol (holding potential 0 mV, from -120 mV to +120 mV) was applied. The current was not blocked by apamin, TRAM-34 and iberiotoxin, the small, intermediate and big-conductance Ca(2+) -activated K(+) channel blockers, and it was not sensitive to the pipette solution chelated with EGTA. CORM2 still activated the current when the chloride in the pipette solution was substituted by equal mol gluconic acid. Substitution of the sodium in the bath with choline significantly reduced the current activated by CORM2. The current was regarded as the non-selective cation current. The current showed slightly inward rectifier property and was not sensitive to Gd(3+) (100 microM), La(3+) (10 microM) or 2-aminoethoxydiphenyl borate (100 microM). CO (10 microM), CORM3 (100, 200 microM) and RuCl(3) (100 microM) were used as controls and showed no effect of the current activation. In conclusion, CORM2 activated the non-selective cation current in HUVECs independently of its CO releasing.
authors.affiliation: Department of Pharmacology, State-Province Key Laboratories of Biomedicine and Pharmaceutics, Harbin Medical University, Harbin 150081, PR China. dldong@tom.com
authors.forename: De-Li
authors.initials: DL
authors.lastname: Dong
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Zhang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
mesh_terms: D002118:Calcium / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects*; D012428:Ruthenium / Q000494:pharmacology*
chemical_list: D009942:Organometallic Compounds; D024681:Potassium Channels, Calcium-Activated; C447082:tricarbonyldichlororuthenium (II) dimer; D007811:Lanthanum; D002248:Carbon Monoxide; D012428:Ruthenium; D005682:Gadolinium; D002118:Calcium