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J. Biol. Chem., Vol. 279, Issue 21, 21815-21823, May 21, 2004

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Involvement of Sodium in Early Phosphatidylserine Exposure and Phospholipid Scrambling Induced by P2X7 Purinoceptor Activation in Thymocytes^*

Marie-Pierre Courageot, Sandrine Lépine, Michel Hours¶, Françoise Giraud, and Jean-Claude Sulpice||

From the Laboratoire des Biomembranes et Messagers Cellulaires, CNRS UMR 8619 and ^¶Service de cytométrie, Institut Fédératif de Recherches 46, bât 440, Université Paris XI, 91405 Orsay Cedex, France

Extracellular ATP (ATP_ec), a possible effector in thymocyte selection, induces thymocyte death via purinoceptor activation. We show that ATP_ec induced cell death by apoptosis, rather than lysis, and early phosphatidylserine (PS) exposure and phospholipid scrambling in a limited thymocyte population (35–40%). PS externalization resulted from the activation of the cationic channel P2X7 (formerly P2Z) receptor and was triggered in all thymocyte subsets although to different proportions in each one. Phospholipid movement was dependent on ATP_ec-induced Ca²⁺ and/or Na⁺ influx. At physiological external Na⁺ concentration, without external Ca²⁺, PS was exposed in all ATP_ec-responsive cells. In contrast, without external Na⁺, physiological external Ca²⁺ concentration promoted a submaximal response. Altogether these data show that Na⁺ influx plays a major role in the rapid PS exposure induced by P2X7 receptor activation in thymocytes.

Received for publication, February 9, 2004 , and in revised form, March 2, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a grant from the Association de la Recherche contre le Cancer (ARC).

^|| To whom correspondence should be addressed. Tel.: 33-01-69-15-49-59; Fax: 33-01-69-15-49-61; E-mail: Jean-Claude.Sulpice{at}ibaic.u-psud.fr.

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