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

Abstract

AIM: To study the effects of palmatine, a known inhibitor on delayed rectifier potassium current and L-type calcium current (I_Ca,L) in guinea pig ventricular myocytes, on the potassium and calcium currents in isolated rat hepatocytes. METHODS: Tight-seal whole-cell patch-clamp techniques were performed to investigate the effects of palmatine on the delayed outward potassium currents (I_K), inward rectifier potassium current (I_K1) and Ca²⁺ release-activated Ca²⁺ current (I_CRAC) in enzymatically isolated rat hepatocytes. RESULTS: Palmatine 0.3-100 μM reduced I_K in a concentration-dependent manner with EC₅₀ of 41.62 ± 10.11 μM and nH, 0.48 ± 0.07 (n = 8). The effect of the drug was poorly reversible after washout. When the bath solution was changed to tetraethylammonium (TEA) 8 mM, I_K was inhibited. Palmatine 10 μM and 100 μM shifted the I-V curves of I_K downward, and the block of I_K was voltage-independent. Palmatine 0.3-100 μM also inhibited I_CRAC in a concentration-dependent manner. The fitting parameters were as follows: EC₅₀ = 51.19 ± 15.18 mM, and n_H = 0.46 ± 0.07 (n = 8). The peak value of I_CRAC in the I-V relationship was decreased by palmatine 10 μM and 100 μM. But the reverse potential of I_CRAC occurred at Voltage = 0 mV in all cells. Palmatine 0.3-100 μM failed to have any significant effect on either inward or outward components of I_K1 at any membrane potential examined. CONCLUSION: The inhibitory effects on I_K and I_CRAC could be one of the mechanisms that palmatine exerts protective effect on hepatocytes.