Inhibitory effects of berberine on voltage- and calcium-activated potassium currents in human myeloma cells

The effects of berberine, an isoquinoline alkaloid, were investigated in human myeloma cells. In cells with intracellular Ca²⁺ concentration ([Ca²⁺](i)) = 10 nM, the depolarizing square pulses from -80 mV elicited an instantaneous outward current with an inactivation. This outward current was voltage dependent, activating at -30 mV and showed inactivation with repetitive depolarization, and was hence believed to be n type voltage- activated K⁺ current (I(K(v))). Berberine (30 μM) produced a prolongation in the recovery of I(K(v)) inactivation. In cells with [Ca²⁺](i) = 1 μM, berberine also inhibited A23187-induced I(K(Ca)). Berberine (1-300 μM) caused the inhibition of I(k(v)) and I(K(Ca)) in the concentration-dependent manners. The IC₅₀ values of berberine-induced inhibition of I(K(v)) and I(K(Ca)) were approximately 15 μM and 50 μM, respectively. In inside-out configurations, berberine inside the pipette suppressed the activity of K(Ca) channels without changing the single channel conductance. Berberine also inhibited the proliferation of this cell line and the IC₅₀ value of berberine-induced inhibition of cell proliferation was 5 μM. Thus, the cytotoxic effect of berberine in cancer cells may be partially explained by its direct blockade of these K⁺ channels.