New insights into maitotoxin action.
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 microM verapamil, 1 microM nifedipine or 1 mM La3+ but was blocked by Zn2+ (IC50 = 41 microM). 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 microM). 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 alpha-latrotoxin, others those of pore-forming agents such as melittin or alpha-toxin of Staphylococcus aureus.
Sladeczek
F
F
Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médical, Centre de Pharmacologie-Endocrinologie, Montpellier, France.
Schmidt
B H
BH
Alonso
R
R
Vian
L
L
Tep
A
A
Yasumoto
T
T
Cory
R N
RN
Bockaert
J
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007477:Ions; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D035964:Oxocins; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013403:Sugar Phosphates / Q000096:biosynthesis*; D000095702:Polyether Toxins
D002118:Calcium; D002121:Calcium Channel Blockers; D007295:Inositol Phosphates; D007477:Ions; D008387:Marine Toxins; D035964:Oxocins; D011188:Potassium; D012964:Sodium; D013403:Sugar Phosphates; C020394:maitotoxin; D000095702:Polyether Toxins