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(Circulation Research. 2004;95:e11.)
© 2004 American Heart Association, Inc.

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Subcortical Ca²⁺ Waves Sneaking Under the Plasma Membrane in Endothelial Cells

Masashi Isshiki, Akiko Mutoh, Toshiro Fujita

From the Department of Nephrology and Endocrinology, Faculty of Medicine, Tokyo University, Tokyo, Japan.

Correspondence to M. Isshiki, Department of Nephrology and Endocrinology, Faculty of Medicine, Tokyo University, Tokyo 113-8655, Japan. E-mail isshiki-tky{at}umin.ac.jp

Subplasmalemmal Ca²⁺, dynamically equilibrated with extracellular Ca²⁺, affects numerous signaling molecules, effectors, and events within this restricted space. We demonstrated the presence of a novel Ca²⁺ wave propagating beneath the plasma membrane in response to acute elevation of extracellular [Ca²⁺], by targeting a Ca²⁺ sensor, cameleon, to the endothelial plasmalemma. These subcortical waves, spatially distinct from classical cytosolic Ca²⁺ waves, originated in localized regions and propagated throughout the subplasmalemma. Translocation of an expressed GFP fused with a PH domain of PLC from the plasma membrane to the cytosol accompanied these subcortical waves, and U73122 attenuated not only the GFP-PH translocation, but also the peak amplitude of the subcortical Ca²⁺ waves; this finding suggests the involvement of local IP₃ production through PLC-mediated PIP₂ hydrolysis in the initiation of these waves. Changes in NO production as well as PKCß-GFP translocation from the cytosol to the plasma membrane, but not of GFP-PLA₂ to perinuclear endomembranes, were associated with the subplasmalemmal Ca²⁺ changes. Thus, extracellular Ca²⁺ maintains the basal PLC activity of the plasma membrane, is involved in the initiation of compartmentalized subcortical Ca²⁺ waves, and regulates Ca²⁺-dependent signaling molecules residing in or translocated to the plasma membrane. The full text of this article is available online at http://circres.ahajournals.org.

Key Words: subplasmalemmal Ca²⁺ • FRET • cameleon • endothelium • phospholipase C

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