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(Circulation Research. 2005;97:1209.)
© 2005 American Heart Association, Inc.

Editorials

EDHF Redux: EETs, TRPV4, and Ca²⁺ Sparks

Michael I. Kotlikoff

From the Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.

Correspondence to Michael I. Kotlikoff, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail mik7@cornell.edu

See related article, pages 1270–1279

Key Words: K channel • ryanodine receptor • EET • epoxygenase

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Over the past two decades the complexity of the molecular processes underlying endothelial-dependent vascular relaxation has gradually become apparent. After the ground breaking discovery of the role of NO as a major endothelium-derived relaxant factor (EDRF), evidence emerged indicating the existence of a hyperpolarizing factor (endothelium-derived hyperpolarizing factor [EDHF]) with actions distinct from the cyclase-dependent relaxations associated with endothelial production of NO and prostacyclin.^1–3 The specific molecules and vascular relaxation mechanisms underlying this intensely studied phenomenon have been difficult to establish, however. H₂O₂, K ions, and epoxygenase products have all been implicated as the EDHF, and evidence has suggested in turn that the mechanism by which EDHF relaxes arteries involves diffusion of the substance to smooth muscle and direct gating effects on calcium-activated K⁺ (maxiK) channels,^4,5 actions mediated through endothelial small and intermediate conductance Ca²⁺-activated K⁺ (SK and IK) channels,^6–8 and passive ionic effects associated with an extracellular accumulation of K⁺ ions.⁹ To further muddy these dark waters, recent evidence has implicated TRPV4 channels in EDHF signaling in several vascular preparations. In this issue of Circulation Research, Earley and colleagues¹⁰ identify a new putative mechanism and one that links EDHF to the regulation of Ca²⁺ release by ryanodine receptors (RYR), thereby forging a mechanistic link between EDHF and the well described local gating of large conductance Ca²⁺-activated K⁺ (maxiK) channels by Ca²⁺ sparks.¹¹

Several lines of evidence in diverse vascular beds have implicated endothelial epoxygenase products in the process of endothelial hyperpolarization.^12,13 While multifunctional cytochrome . . . [Full Text of this Article]

Related Article:

TRPV4 Forms a Novel Ca²⁺ Signaling Complex With Ryanodine Receptors and BK_Ca Channels

Scott Earley, Thomas J. Heppner, Mark T. Nelson, and Joseph E. Brayden
Circ. Res. 2005 97: 1270-1279. [Abstract] [Full Text] [PDF]

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