maitotoxin and barium-chloride

Maitotoxin (MTX) is a potent marine toxin isolated from the toxic dinoflagellate, Gambierdiscus toxicus. We have examined the possibility of MTX activating calcium channels using cultured neuroblastoma cells (N1E-115). MTX (10 ng/ml) produced a depolarization of the membrane, which was prevented by the removal of Ca2+ from the external medium. Under voltage clamp conditions, membrane currents were recorded with 50 mM Ba2+ as a charge carrier through calcium channels. After application of MTX (1 ng/ml), an inward current necessary to hold the membrane at -90 mV increased progressively. This was followed by a gradual decrease of the transient inward Ba2+ current through type I calcium channels recorded at -30 mV which was eventually abolished. A similar tendency was observed in the long-lasting inward Ba2+ current through type II calcium channels, which was recorded at +10 mV. The MTX action was antagonized by calcium channel blockers such as verapamil (100 microM) and La3+ (1 mM). A high concentration of verapamil (500 microM) blocked both types of calcium channels persistently. After washout of verapamil but while the calcium channels were still blocked, MTX (1 ng/ml) induced a steady-state current. The MTX-induced current showed an inward-rectifying property with a reversal potential of approximately -30 mV. The results suggest that the MTX-induced current does not flow through calcium channels. Thus, MTX may create a pore in the membrane with pharmacological properties similar to those of calcium channels.

Topics: Animals; Barium; Barium Compounds; Cell Line; Cell Membrane; Chlorides; Ion Channels; Marine Toxins; Membrane Potentials; Mice; Neuroblastoma; Oxocins; Verapamil