AIM: To study the effects of AP-Q on CCl4-induced acute liver injury, delayed outward potassium current (Iκ), inward rectifier potassium current (Iκ1) and calcium release-activated calcium current (ICRAC) in isolate...AIM: To study the effects of AP-Q on CCl4-induced acute liver injury, delayed outward potassium current (Iκ), inward rectifier potassium current (Iκ1) and calcium release-activated calcium current (ICRAC) in isolated rat hepatocytes. METHODS: A single dose of CCl4 (10 μg/mL, ip) was injected to induce acute liver injury in rats. Serum aminotransferase activities were determined. Whole cell patch-clamp techniques were used to investigate the effects of AP-Q on delayed outward potassium current (Iκ), inward rectifier potassium current (IKI) and calcium release-activated calcium current (ICRAC). RESULTS: AP-Q (3.5 and 7 μg/kg) pretreatment significantly reduced ALT and AST activities. AP-Q 0.1-100 nM produced a concentration-dependent increase of Iκ with EC50 value of 5.55±1.8 nM (n=6). AP-Q 30 nM shifted the I-V curve of Iκ leftward and upward. CCl4 4 mM decreased Iκ current 28.6±0.5% at 140 mV. After exposure to CCl4 for 5 rain, AP-Q 30 nM attenuated the decrease of Iκ induced by CCl4 close to normal amplitude. AP-Q 0.01-100 nM had no significant effect on either inward or outward components of Iκ1 at any membrane potential examined. AP-Q 0.1-100 nM had no significant influence on the peak amplitude of ICRAC, either,and did not affect the shape of its current voltage curve. CONCLUSION: AP-Q has a protective effect on CCl4-induced liver injury, probably through selectively increased Iκ in hepatocytes.展开更多
文摘AIM: To study the effects of AP-Q on CCl4-induced acute liver injury, delayed outward potassium current (Iκ), inward rectifier potassium current (Iκ1) and calcium release-activated calcium current (ICRAC) in isolated rat hepatocytes. METHODS: A single dose of CCl4 (10 μg/mL, ip) was injected to induce acute liver injury in rats. Serum aminotransferase activities were determined. Whole cell patch-clamp techniques were used to investigate the effects of AP-Q on delayed outward potassium current (Iκ), inward rectifier potassium current (IKI) and calcium release-activated calcium current (ICRAC). RESULTS: AP-Q (3.5 and 7 μg/kg) pretreatment significantly reduced ALT and AST activities. AP-Q 0.1-100 nM produced a concentration-dependent increase of Iκ with EC50 value of 5.55±1.8 nM (n=6). AP-Q 30 nM shifted the I-V curve of Iκ leftward and upward. CCl4 4 mM decreased Iκ current 28.6±0.5% at 140 mV. After exposure to CCl4 for 5 rain, AP-Q 30 nM attenuated the decrease of Iκ induced by CCl4 close to normal amplitude. AP-Q 0.01-100 nM had no significant effect on either inward or outward components of Iκ1 at any membrane potential examined. AP-Q 0.1-100 nM had no significant influence on the peak amplitude of ICRAC, either,and did not affect the shape of its current voltage curve. CONCLUSION: AP-Q has a protective effect on CCl4-induced liver injury, probably through selectively increased Iκ in hepatocytes.
