Effects of Ca2+ channel blockers on store-operated Ca2+ channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats.
OBJECTIVE
To study the effects of hepatic ischemia/reperfusion (I/R) injury on store-operated calcium channel (SOC) currents (I(SOC)) in freshly isolated rat Kupffer cells, and the effects of Ca(2+) channel blockers, 2-aminoethoxydiphenyl borate (2-APB), SK and F96365, econazole and miconazole, on I(SOC) in isolated rat Kupffer cells after hepatic I/R injury.


METHODS
The model of rat hepatic I/R injury was established. Whole-cell patch-clamp techniques were performed to investigate the effects of 2-APB, SK and F96365, econazole and miconazole on I(SOC) in isolated rat Kupffer cells after hepatic I /R injury.


RESULTS
I/R injury significantly increased I(SOC) from -80.4 +/- 25.2pA to -159.5 +/- 34.5pA ((b)P < 0.01, n = 30). 2-APB (20, 40, 60, 80, 100 micromol/L), SK and F96365 (5, 10, 20, 40, 50 micromol/L), econazole (0.1, 0.3, 1, 3, 10 micromol/L) and miconazole (0.1, 0.3, 1, 3, 10 micromol/L) inhibited I(SOC) in a concentration-dependent manner with IC50 of 37.41 micromol/L (n = 8), 5.89 micromol/L (n = 11), 0.21 micromol/L (n = 13), and 0.28 micromol/L (n = 10). The peak value of I(SOC) in the I-V relationship was decreased by the blockers in different concentrations, but the reverse potential of I(SOC) was not transformed.


CONCLUSIONS
SOC is the main channel for the influx of Ca(2+) during hepatic I/R injuries. Calcium channel blockers, 2-APB, SK and F96365, econazole and miconazole, have obviously protective effects on I/R injury, probably by inhibiting I(SOC) in Kupffer cells and preventing the activation of Kupffer cells.
Jiang
Nan
N
Department of General Surgery, Digestive Medical Center, First Affiliated Hospital of Tsinghua University, Beijing 100016, China.
Zhang
Zong-Ming
ZM
Liu
Liang
L
Zhang
Chi
C
Zhang
Yan-Lu
YL
Zhang
Zi-Chao
ZC
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004464:Econazole / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007728:Kupffer Cells / Q000473:pathology / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D004464:Econazole; D008825:Miconazole; C109986:2-aminoethoxydiphenyl borate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole