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Biochem J. Jul 15, 1994; 301(Pt 2): 437–441.
PMCID: PMC1137099

Maitotoxin activates cation channels distinct from the receptor-activated non-selective cation channels of HL-60 cells.


We investigated whether maitotoxin activates non-selective cation channels, as was recently proposed [Soergel, Yasumoto, Daly and Gusovsky (1992) Mol. Pharmacol. 41, 487-493]. Stimulation of dibutyryl cyclic AMP-differentiated HL-60 cells with the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 0.1 microM), the Ca(2+)-ATPase inhibitor thapsigargin (0.1 microM) or maitotoxin (25 ng/ml) resulted in an increase in cytoplasmic free calcium concentration ([Ca2+]i). Unlike fMLP and thapsigargin, maitotoxin produced no increase in [Ca2+]i in the absence of extracellular Ca2+. The increase in [Ca2+]i induced by fMLP was blocked by pretreatment with pertussis toxin (100 ng/ml for 24 h) but not that induced by maitotoxin. Similarly, the increase in [Ca2+]i produced by fMLP but not that produced by maitotoxin was inhibited by pretreatment with phorbol myristate acetate (100 ng/ml). Both fMLP- and maitotoxin-induced increases in [Ca2+]i were blocked by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl)-1H-imid azole hydrochloride (SKF 96365) in a concentration-dependent manner. However, the maitotoxin-induced increase in [Ca2+]i was more sensitive to inhibition by SKF 96365 than the fMLP-induced increase. fMLP-induced increases in [Ca2+]i were blocked by cations with Gd3+ being more effective than Cd2+, whereas for maitotoxin Cd2+ was more effective than Gd3+. Both fMLP and thapsigargin stimulated quenching of Fura-2 fluorescence in the presence of extracellular Mn2+, whereas maitotoxin produced no Mn2+ quenching. Taken together these results suggest that maitotoxin does not stimulate the nonselective cation channel activated by fMLP, but instead activates Ca2+ influx by a different mechanism.

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  • Berta P, Sladeczek F, Derancourt J, Durand M, Travo P, Haiech J. Maitotoxin stimulates the formation of inositol phosphates in rat aortic myocytes. FEBS Lett. 1986 Mar 3;197(1-2):349–352. [PubMed]
  • Chaplinski TJ, Niedel JE. Cyclic nucleotide-induced maturation of human promyelocytic leukemia cells. J Clin Invest. 1982 Nov;70(5):953–964. [PMC free article] [PubMed]
  • Choi OH, Padgett WL, Nishizawa Y, Gusovsky F, Yasumoto T, Daly JW. Maitotoxin: effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells. Mol Pharmacol. 1990 Feb;37(2):222–230. [PubMed]
  • Columbo M, Taglialatela M, Warner JA, MacGlashan DW, Jr, Yasumoto T, Annunziato L, Marone G. Maitotoxin, a novel activator of mediator release from human basophils, induces large increases in cytosolic calcium resulting in histamine, but not leukotriene C4, release. J Pharmacol Exp Ther. 1992 Dec;263(3):979–986. [PubMed]
  • Demaurex N, Lew DP, Krause KH. Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells. J Biol Chem. 1992 Feb 5;267(4):2318–2324. [PubMed]
  • Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed]
  • Gusovsky F, Daly JW. Maitotoxin: a unique pharmacological tool for research on calcium-dependent mechanisms. Biochem Pharmacol. 1990 Jun 1;39(11):1633–1639. [PubMed]
  • Gusovsky F, Bitran JA, Yasumoto T, Daly JW. Mechanism of maitotoxin-stimulated phosphoinositide breakdown in HL-60 cells. J Pharmacol Exp Ther. 1990 Feb;252(2):466–473. [PubMed]
  • Hamilton SL, Perez M. Toxins that affect voltage-dependent calcium channels. Biochem Pharmacol. 1987 Oct 15;36(20):3325–3329. [PubMed]
  • Kobayashi M, Miyakoda G, Nakamura T, Ohizumi Y. Ca-dependent arrhythmogenic effects of maitotoxin, the most potent marine toxin known, on isolated rat cardiac muscle cells. Eur J Pharmacol. 1985 Apr 23;111(1):121–123. [PubMed]
  • Krautwurst D, Seifert R, Hescheler J, Schultz G. Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production. Biochem J. 1992 Dec 15;288(Pt 3):1025–1035. [PMC free article] [PubMed]
  • Krautwurst D, Hescheler J, Arndts D, Lösel W, Hammer R, Schultz G. Novel potent inhibitor of receptor-activated nonselective cation currents in HL-60 cells. Mol Pharmacol. 1993 May;43(5):655–659. [PubMed]
  • Merritt JE, Jacob R, Hallam TJ. Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. J Biol Chem. 1989 Jan 25;264(3):1522–1527. [PubMed]
  • Merritt JE, Armstrong WP, Benham CD, Hallam TJ, Jacob R, Jaxa-Chamiec A, Leigh BK, McCarthy SA, Moores KE, Rink TJ. SK&F 96365, a novel inhibitor of receptor-mediated calcium entry. Biochem J. 1990 Oct 15;271(2):515–522. [PMC free article] [PubMed]
  • Murata M, Gusovsky F, Yasumoto T, Daly JW. Selective stimulation of Ca2+ flux in cells by maitotoxin. Eur J Pharmacol. 1992 Sep 1;227(1):43–49. [PubMed]
  • Ohizumi Y, Yasumoto T. Contractile response of the rabbit aorta to maitotoxin, the most potent marine toxin. J Physiol. 1983 Apr;337:711–721. [PMC free article] [PubMed]
  • Schettini G, Koike K, Login IS, Judd AM, Cronin MJ, Yasumoto T, MacLeod RM. Maitotoxin stimulates hormonal release and calcium flux in rat anterior pituitary cells in vitro. Am J Physiol. 1984 Oct;247(4 Pt 1):E520–E525. [PubMed]
  • Schwaner I, Seifert R, Schultz G. Receptor-mediated increases in cytosolic Ca2+ in the human erythroleukaemia cell line involve pertussis toxin-sensitive and -insensitive pathways. Biochem J. 1992 Jan 15;281(Pt 2):301–307. [PMC free article] [PubMed]
  • Seifert R, Schächtele C. Studies with protein kinase C inhibitors presently available cannot elucidate the role of protein kinase C in the activation of NADPH oxidase. Biochem Biophys Res Commun. 1988 Apr 29;152(2):585–592. [PubMed]
  • Seifert R, Serke S, Huhn D, Bessler WG, Hauschildt S, Metzger J, Wismüller KH, Jung G. Incomplete functional differentiation of HL-60 leukemic cells by synthetic lipopeptides. Partial inhibition by pertussis toxin of enhanced superoxide formation. Eur J Biochem. 1992 Jan 15;203(1-2):143–151. [PubMed]
  • Sladeczek F, Schmidt BH, Alonso R, Vian L, Tep A, Yasumoto T, Cory RN, Bockaert J. New insights into maitotoxin action. Eur J Biochem. 1988 Jul 1;174(4):663–670. [PubMed]
  • Smith CD, Uhing RJ, Snyderman R. Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leukocytes is disrupted by phorbol esters. J Biol Chem. 1987 May 5;262(13):6121–6127. [PubMed]
  • Soergel DG, Yasumoto T, Daly JW, Gusovsky F. Maitotoxin effects are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry. Mol Pharmacol. 1992 Mar;41(3):487–493. [PubMed]
  • Takahashi M, Tatsumi M, Ohizumi Y, Yasumoto T. Ca2+ channel activating function of maitotoxin, the most potent marine toxin known, in clonal rat pheochromocytoma cells. J Biol Chem. 1983 Sep 25;258(18):10944–10949. [PubMed]
  • Watanabe A, Ishida Y, Honda H, Kobayashi M, Ohizumi Y. Ca(2+)-dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate. Br J Pharmacol. 1993 May;109(1):29–36. [PMC free article] [PubMed]

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