Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Blood Cells Molecules and Diseases 1-9 ciguatoxins red blood cells cell swelling L type Ca2+ channels nitric oxide nitric oxide synthase soluble guanylate cyclase cytochalasin D 2006 fdi:010051883 ENG Blood Cells Molecules and Diseases 1079-9796 CC:0002348800-0001 1 10.1016/j.bcmd.2005.10.007 https://www.documentation.ird.fr/hor/fdi:010051883 https://www.documentation.ird.fr/intranet/publi/depot/2011-06-01/010051883.pdf 36 Horizon (IRD) 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. 020 ; 050