Inhibitory effects of berberine on ion channels of rat hepatocytes

AIM: To examine the effects of berberine, an isoquinoline alkaloid with a long history used as a tonic remedy for liver and heart, on ion channels of isolated rat hepatocytes.METHODS: Tight-seal whole-cell patch-clamp techniques were performed to investigate the effects of berberine on the delayed outward potassium currents (Ik), inward rectifier potassium currents (Ik1) and Ca^2+ release-activated Ca^+ currents (ICRAC) in enzymatically isolated rat hepatocytes.RESULTS: Berbenne 1-300 μmol/L reduced/K in a concentration-dependent manner with EC50 of 38.86=1=5.37 μmol/L and nH of 0.82±0.05 (n = 8). When the bath solution was changed to tetraethylammonium (TEA) 8 retool/L,IK was inhibited.Berberine 30 μmol/L reduced/K at all examined membranepote ntials, especially at potentials positive to +60 mV (n = 8,P<0.05 or P<0.01 vs control). Berberine had mild inhibitory effects on IK1 in rat hepatocytes. Berberine 1-300 μmol/L also inhibited ICRAC in a concentration-dependent fashion. The fitting parameters were EC50 = 47.20±10.86 μmol/L,nH= 0.71±0.09 (n = 8). The peak value of/CRAC in the I-Vrelationship was decreased by berberine 30 μmol/L at potentialnegative to -80 mV (n = 8, P<0.05 vscontrol). But the reverse potential of/CRAC occurred at voltage 0 mV in all cells.CONCLUSION: Berberine has inhibitory effects on potassium and calcium currents in isolated rat hepatocytes, which may be involved in hepatoprotection.

Effects of palmatine on potassium and calcium currents in isolated rat hepatocytes

AIM: To study the effects of palmatine, a known inhibitoron delayed rectifier potassium current and L-type calciumcurrent (ICa,L) in guinea pig ventricular myocytes, on thepotassium and calcium currents in isolated rat hepatocytes.METHODS: Tight-seal wh ole-cell patch-clamp techniqueswere performed to investigate the effects of palmatine onthe delayed outward potassium currents (IK), inward rectifierpotassium current (IK1) and Ca2+ release-activated Ca2+current (ICRAC) in enzymatically isolated rat hepatocytes.RESULTS: Palmatine 0.3-100 μM reduced IK in a concentationdependent manner with EC50of 41.62±10.11 μM and nH,0.48±0.07 (n=8). The effect of the drug was poorly reversibleafter washout. When the bath solution was changed totetraethylammonium (TEA) 8 mM, IK was inhibited.Palmatine 10 μM and 100 μM shifted the I-V curves of IKdownward, and the block of IK was voltage-independent.Palmatine 0.3-100 μM also inhibited ICRAC in a concentration-dependent manner. The fitting parameters were as follows:ECs0=51.19±15.18 μM, and nH=0.46+0.07 (n=8). The peakvalue of ICRAC in the I-V relationship was decreased bypalmatine 10 μM and 100 μM. But the reverse potential ofIcRAcoCcurred at Voltage=0 mV in all cells. Palmatine 0.3-100 μM failed to have any significant effect on either inwardor outward components of IK1 at any membrane potentialexamined.CONCLUSION: The inhibitory effects on IK and ICRAC couldbe one of the mechanisms that palmatine exerts protectiveeffect on hepatocytes.

Electrophysiological effects of anthopleurin-Q on rat hepatocytes

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.