INHIBITORY EFFECTS OF BERBERINE ON VOLTAGE-ACTIVATED AND CALCIUM-ACTIVATED POTASSIUM CURRENTS NN 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 elicit ed an instantaneous outward current with an inactivation. This outward current was voltage dependent, activating at -30 mV and showed inacti vation with repetitive depolarization, and was hence believed to be n type voltage-activated K+ current (I-K(V)). Berberine (30 mu M) produc ed a prolongation in the recovery of I-K(V) inactivation. In cells wit h [Ca2+](i) = 1 mu M, berberine also inhibited A23187-induced I-K(Ca). Berberine(1-300 mu M) caused the inhibition of IK(V) and IK(Ca) in th e concentration-dependent manners. The IC50 values of berberine-induce d inhibition of I-K(V) and I-K(Ca) were approximately 15 mu M and 50 m u M, 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 mu M. Thus, the cytotoxic effect of berber ine in cancer cells may be partially explained by its direct blockade of these K+ channels.