Enhancing effects of diethyldithiocarbamate on increase of sodium channel by sulfur dioxide derivatives in ventricular myocytes.
The enhancing effects of diethyldithiocarbamate (DDC) on increase of sodium channel by sulfur dioxide derivatives in ventricular myocytes were studied using the whole cell patch-clamp technique to probe the mechanism of SO2 on the cardiovascular system in this study. Firstly, the effects of DDC and/or sulfur dioxide (SO2) derivatives on the activities of superoxide dismutase (SOD) were studied. The results showed that DDC decreased SOD activities significantly and SO2 derivatives had no significant effect on SOD activities; however, DDC and SO2 derivatives combined led to a significant decrease of SOD activities. In the electrophysiological test, DDC (1-100 mM) increased sodium current (INa) in a concentration-dependent manner and the concentration for half-maximum increase (EC50) was 20 mM. Addition of 20 mM DDC to the SO2 derivatives-containing medium significantly shifted the voltage-dependent activation curve of INa toward the hyperpolarizing direction (Vh are -51 mV, -53 mV and -54 mV, respectively) and shifted the steady-state inactivation curve to more positive potentials (Vh are -74 mV, -71 mV and -65 mV, respectively) compared with the control and 10 microM SO2 derivatives exposure. These results indicated that DDC could enhance the increasing effects on Na+ channels induced by SO2 derivatives, and suggested that the toxicity of SO2 on ventricular myocytes of rats was realized by free radical, especially O2-.
Wei
Haiying
H
Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, PR China. weihaiying@sxu.edu.cn
Meng
Ziqiang
Z
D000818:Animals; D004050:Ditiocarb / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology* / Q000201:enzymology; D015640:Ion Channel Gating / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000378:metabolism*; D013458:Sulfur Dioxide / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D015222:Sodium Channels; D013458:Sulfur Dioxide; D004050:Ditiocarb; D013482:Superoxide Dismutase