Palytoxin-induced increase in cytosolic-free Ca(2+) in mouse spleen cells.

ABSTRACT

The effect of palytoxin (C(129)H(223)N(3)O(54)) on Ca(2+) homeostasis in immune cells has not been studied. Therefore, we investigated the effect of palytoxin on the cytosolic-free Ca(2+) concentration ([Ca(2+)](i)) in mouse spleen cells using a fluorescence Ca(2+) indicator, fura-2. Palytoxin (0.1-100 nM) increased [Ca(2+)](i) in a concentration-dependent manner. The palytoxin-induced increase in [Ca(2+)](i) was abolished by the omission of extracellular Ca(2+) or 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF-96365, 100 microM), and was greatly inhibited by Ni(2+) (2 mM). Ouabain (0.5-1 mM) partially inhibited the palytoxin-induced response. There was no effect of decreased extracellular Na(+) (6.2 mM), tetrodotoxin (1 microM), verapamil (10 microM), nifedipine (10 microM), omega-agatoxin IVA (200 nM), omega-conotoxin GVIA (1 microM), omega-conotoxin MVIIC (500 nM), or La(3+) (100 microM). These results suggest that palytoxin increases [Ca(2+)](i) in mouse spleen cells by stimulating Ca(2+) entry through an SKF-96365-, Ni(2+)-sensitive pathway.