Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins Sauviat, M.P. /Boydron Le Garrec, Raphaëlle Masson, J.B. Lewis, R.L. Vernoux, J.P. Molgo, J. /Laurent, Dominique Benoit, E. ciguatoxins red blood cells cell swelling L type Ca2+ channels nitric oxide nitric oxide synthase soluble guanylate cyclase cytochalasin D 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 mu M) induced RBC swelling within 60 min. The CTXs-induced RBC swelling was blocked by apamin (1 mu M) and by Sr2+ (1 mu M). P-CTX-1-induced RBC swelling was prevented and inhibited by H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one(27 mu M), an inhibitor Of Soluble guanylate cyclase (sGC), and NOS blockade by NG methyl-L-arginine (L-NMA; 10 mu M). Cytochalasin D (cytD, 10 mu M) 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. (c) 2005 Elsevier Inc. All rights reserved. 2006 text https://www.documentation.ird.fr/hor/fdi:010051883 fdi:010051883 Sauviat M.P., Boydron Le Garrec Raphaëlle, Masson J.B., Lewis R.L., Vernoux J.P., Molgo J., Laurent Dominique, Benoit E.. Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins. 2006, 36 (1), 1-9 EN