Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins

Abstract : The mechanisms underlying the swelling of frog red blood cells (RBC), induced by Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins (CTXs), were investigated by measuring the length, width and surface of their elliptic shape. P-CTX-1 (0.5 to 5 nM) and C-CTX-1 (1 nM) induced RBC swelling within 60 min. The CTXs-induced RBC swelling was blocked by apamin (1 μM) and by Sr2+ (1 mM). P-CTX-1-induced RBC swelling was prevented and inhibited by H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (27 μM), an inhibitor of soluble guanylate cyclase (sGC), and NOS blockade by NG methyl-l-arginine (l-NMA; 10 μM). Cytochalasin D (cytD, 10 μM) increased RBC surface and mimicked CTX effect but did not prevent the P-CTX-1-induced l-NMA-sensitive extra increase. Calculations revealed that P-CTX-1 and cytD increase RBC total surface envelop and volume. These data strongly suggest that the molecular mechanisms underlying CTXs-induced RBC swelling involve the NO pathway by an activation of the inducible NOS, leading to sGC activation which modulates intracellular cGMP and regulates L-type Ca2+ channels. The resulting increase in intracellular Ca2+ content, in turn, disrupts the actin cytoskeleton, which causes a water influx and triggers a Ca2+-activated K+ current through SK2 isoform channels.
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Submitted on : Wednesday, July 26, 2006 - 4:35:24 PM
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Martin-Pierre Sauviat, Raphaële Boydron-Le Garrec, Jean-Baptiste Masson, Richard L. Lewis, Jean-Paul Vernoux, et al.. Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins. Blood Cells, Molecules and Diseases, Elsevier, 2006, 36(1), pp.1-9. ⟨10.1016/j.bcmd.2005.10.007⟩. ⟨hal-00087786⟩



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