Toxin of the marine alga Prymnesium patelliferum enhances voltage dependent Ca(2+)-currents, elevates the cytosolic Ca(2+)-concentration and facilitates hormone release in clonal rat pituitary cells.
The marine flagellate Prymnesium patelliferum produces toxins lethal to fish. The toxin extracted from the alga has haemolytic, cytotoxic and neurotoxic effects, but the action mechanisms of the toxin are not known in detail. We have examined the toxin effects on the voltage sensitive Ca(2+)-currents, the cytosolic Ca(2+)-level ([Ca2+]i) and the prolactin release in clonal rat anterior pituitary GH4C1 cells, which possess T- and L-type Ca(2+)-channels. The trans-membrane Ca(2+)-current was recorded using whole-cell voltage clamp. After 5-15 min exposure to the algal toxin at a final concentration of 50,000-100,000 cells mL-1, the Ca(2+)-currents through both the T- and L-channels showed a 2-3-fold enhancement. The voltage sensitivity of the Ca(2+)-currents was not affected by the algal toxin, and the toxin-induced currents were inhibited by 100 microM of the Ca(2+)-channel blocker D-600. In toxin-exposed cells microfluorometric measurements based on fura-2 revealed an increase of [Ca2+]i from 100-150 to 300-500 nM. This elevation was delayed and partially inhibited by 100 microM D-600. The algal toxin induced prolactin release in a dose-dependent manner, and this effect was inhibited by the Ca(2+)-channel blocker verapamil. We therefore conclude that the toxin of P. patelliferum affects the Ca2+ homeostasis of the pituitary cells by increasing the leak through voltage sensitive Ca(2+)-channels, resulting in increased [Ca2+]i and secretion of prolactin.
Kolderup
J
J
Department of Biology, University of Oslo, Norway.
Meldahl
A S
AS
Eriksen
S
S
Haug
E
E
Fonnum
F
F
Sand
O
O
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D002999:Clone Cells; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D056890:Eukaryota; D005470:Fluorometry; D016257:Fura-2; D008387:Marine Toxins / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D008387:Marine Toxins; D011388:Prolactin; D002118:Calcium; D016257:Fura-2