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Title: Modulation of the extracellular divalent cation-inhibited non-selective conductance in cardiac cells by metabolic inhibition and by oxidants
Authors: Macianskiene, Regina ×
Matejovic, P
Sipido, Karin
Flameng, Willem
Mubagwa, Kanigula #
Issue Date: Jul-2001
Series Title: Journal of Molecular and Cellular Cardiology vol:33 issue:7 pages:1371-85
Abstract: The effect of metabolic inhibition and oxidative stress on the monovalent cation-permeable, extracellular divalent cation-inhibited non-selective conductance was investigated in ventricular myocytes at 22 degrees C. Under whole-cell voltage-clamp, with L-type Ca2+ channels blocked by nifedipine, and K+ currents blocked by Cs+ substitution for K+, removal of Ca2+(o)and Mg2+(o) induced a non-selective current (I(NS-(Ca)o)) in mouse, rabbit and rat cells. Removal of glucose increased I(NS-(Ca)o)in the absence of Ca2+(o) and Mg2+(o), but failed to induce this current in the presence of the divalent cations. Further inhibition of glycolysis by 2-deoxyglucose (DOG; 10 mM, in zero glucose) or of mitochondrial function by rotenone (10 microM) or NaCN (5 mM) also failed to induce I(NS-(Ca)o)in the presence of Ca2+(o) and Mg2+(o). Even when given together, DOG and rotenone did not induce I(NS-(Ca)o) in the presence of divalent cations. Preactivated I(NS-(Ca)o) was increased by the oxidants thimerosal (50 microM), diamide (500 microM) and pCMPS (50 microM). However, none of these drugs nor NEM (1 mM) did elicit I(NS-(Ca)o)in the presence of Ca2+(o) and Mg2+(o). Exposure of rat myocytes to Ag+ induced a current resembling I(NS-(Ca)o) (reversing at -5 mV; blocked by 100 microM Gd3+) even in the presence of divalent cations. The data indicate that metabolic inhibition only regulates activated I(NS-(Ca)o)but does not induce the opening of closed channels, and that small oxidants like Ag+ may induce I(NS-(Ca)o) activation by accessing at sites unavailable for larger molecules.
ISSN: 0022-2828
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiac Surgery
Experimental Cardiology
× corresponding author
# (joint) last author

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