New insights into maitotoxin action

Abstract

Maitotoxin (3 ng/mol) induced a massive uptake of 45Ca2+ into BC3H1 cells. This effect exhibits a lag phase of 3 min. Inositol diphosphate formation occurred concomittantly with the 45Ca2+ uptake but inositol monophosphate formation was found only after a 5‐min delay following toxin addition. Maitotoxin‐induced 45Ca2+ influxes could not be blocked by either 1 μM verapamil, 1 μM nifedipine or 1 mM La3+ but was blocked by Zn2+ (IC50= 41 μM). In addition to inositol phosphate formation and 45Ca2+ uptake, maitotoxin stimulated a large uptake of Na+ and a great loss of K+ in BC3H1 cells. In the absence of Ca2+ (1 mM EGTA) none of the four maitotoxin effects could be detected. After restoration of Ca2+ the maitotoxin effects reappeared even when the toxin itself was no longer present. The divalent cation, Co2+ (1 mM), inhibited ion movements induced by maitotoxin and also digitonin (8.1 μM). The toxin action showed a very pronounced pH dependence. At low pH, maitotoxin was inactive. The dose‐response curves for H+ ion inhibition of maitotoxin‐induced Ca2+ uptake showed a shift to the right when determined in the absence of HCO3‐ and HCO3‐/Cl‐ ions. It was concluded that the primary action of maitotoxin in BC3H1 cells was a pore‐forming or channel‐forming activity of a non‐classical type. Some properties of maitotoxin resemble those of α‐latrotoxin, others those of pore‐forming agents such as melittin or α‐toxin of Staphylococcus aureus. Copyright © 1988, Wiley Blackwell. All rights reserved