Pacific ciguatoxin-1b effect over Na+ and K+ currents, inositol 1,4,5-triphosphate content and intracellular Ca2+ signals in cultured rat myotubes.
1. The action of the main ciguatoxin involved in ciguatera fish poisoning in the Pacific region (P-CTX-1b) was studied in myotubes originated from rat skeletal muscle cells kept in primary culture. 2. The effect of P-CTX-1b on sodium currents at short times of exposure (up to 1 min) showed a moderate increase in peak Na+ current. During prolonged exposures, P-CTX-1b decreased the peak Na+ current. This action was always accompanied by an increase of leakage currents, tail currents and outward Na+ currents, resulting in an intracellular Na+ accumulation. This effect is blocked by prior exposure to tetrodotoxin (TTX) and becomes evident only after washout of TTX. 3. Low to moderate concentrations of P-CTX-1b (2-5 nM) partially blocked potassium currents in a manner that was dependent on the membrane potential. 4. P-CTX-1b (2-12 nM) caused a small membrane depolarization (3-5 mV) and an increase in the frequency of spontaneous action potential discharges that reached in general low frequencies (0.1-0.5 Hz). 5. P-CTX-1b (10 nM) caused a transient increase of intracellular inositol 1,4,5-trisphosphate (IP(3)) mass levels, which was blocked by TTX. 6. In the presence of P-CTX-1b (10 nM) and in the absence of external Ca2+, the intracellular Ca2+ levels show a transient increase in the cytoplasm as well as in the nuclei. The time course of this effect may reflect the action of IP(3) over internal stores activated by P-CTX-1b-induced membrane depolarization.
Hidalgo
Jorge
J
Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Casilla 70005, Correo 7, Santiago, Chile. jhidalgo@machi.med.uchile.cl
Liberona
José Luis
JL
Molgó
Jordi
J
Jaimovich
Enrique
E
D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002922:Ciguatoxins; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D001618:beta-Lactamases / Q000494:pharmacology*
D015221:Potassium Channels; D015222:Sodium Channels; C454647:ciguatoxin 1B (CTX 1B); D002922:Ciguatoxins; D013779:Tetrodotoxin; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D001618:beta-Lactamases