Inhibitory effects of berberine on ion channels of rat hepatocyte

摘要

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 (I_k), inward rectifier potassium currents (I_k1) and Ca~(2+) release-activated Ca~(2+) currents (I_(CRAC)) in enzymatically isolated rat hepatocytes. RESULTS: Berberine 1-300 μmol/L reduced I_k in a concentration-dependent manner with EC_(50) of 38.86±5.37 μmol/L and n_H of 0.82±0.05 (n = 8). When the bath solution was changed to tetraethylammonium (TEA) 8 mmol/L, I_k was inhibited. Berberine 30 μmol/L reduced I_k at all examined membrane potentials, especially at potentials positive to +60 mV (n - 8, P< 0.05 or P < 0.01 vs control). Berberine had mild inhibitory effects on I_(k1) in rat hepatocytes. Berberine 1-300 μmoi/L also inhibited I_(CRAC) in a concentration-dependent fashion. The fitting parameters were EC_(50) = 47.20±10.86 μmol/L, n_H = 0.71±0.09 (n = 8). The peak value of I_(CRAC) in the I-V relationship was decreased by berberine 30 μmol/L at potential negative to -80 mV (n = 8, P< 0.05 vs control). But the reverse potential of I_(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.