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(Circulation Research. 2006;99:462.)
© 2006 American Heart Association, Inc.

Editorials

Realizing Its Potential

The Intermediate Conductance Ca²⁺-Activated K⁺ Channel (K_Ca3.1) and the Regulation of Blood Pressure

Ingrid Fleming

From the Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.

Correspondence to Ingrid Fleming, PhD, Vascular Signalling Group, Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. E-mail fleming@em.uni-frankfurt.de

See related article, pages 537–544

Key Words: endothelium-derived hyperpolarizing factor • hypertension • membrane potential • microcirculation • vasodilatation

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

Local vascular tone is generally determined by a variety of factors such as neurotransmitters released from autonomic nerves, circulating vasoactive compounds, tissue metabolites, and endothelium-derived autacoids. The best characterized autacoids are the potent vasodilators nitric oxide (NO) and prostacyclin (PGI₂) and the vasoconstrictor peptide endothelin-1. Several studies have, however, convincingly demonstrated the existence of an NO/PGI₂-independent component of endothelium-dependent relaxation in various arterial beds, most notably in mesenteric, carotid, cerebral, coronary, and renal arteries. Because the NO/PGI₂-independent vasodilatation originally described was coincident with vascular smooth muscle hyperpolarization and was abolished by depolarizing concentrations of potassium, it was proposed to be mediated by an endothelium-derived hyperpolarizing factor or "EDHF."¹

When the term EDHF was initially coined, researchers expected to be able to identify a specific chemical entity synthesized in, and released from, the endothelium which hyperpolarizes vascular smooth muscle cells and elicits relaxation. However, there does not seem to be a specific EDHF, as at least 3 principal mechanisms have been linked to the EDHF phenomenon: (1) an increase in endothelial [Ca²⁺]_i after cell stimulation triggers the synthesis of a cytochrome P450 metabolite which is essential for the subsequent EDHF-mediated responses; (2) K⁺, released from endothelial cells via Ca²⁺-dependent K⁺ (K⁺_Ca) channels induces smooth muscle hyperpolarization by activating inwardly rectifying K⁺ channels or the Na⁺-K⁺-ATPase on vascular smooth muscle cells; and (3) endothelial cell hyperpolarization is transmitted to the vascular smooth muscle via gap junctions. The strengths and weaknesses of the arguments . . . [Full Text of this Article]

Related Article:

Impaired Endothelium-Derived Hyperpolarizing Factor-Mediated Dilations and Increased Blood Pressure in Mice Deficient of the Intermediate-Conductance Ca²⁺-Activated K⁺ Channel

Han Si, Willm-Thomas Heyken, Stephanie E. Wölfle, Marcin Tysiac, Rudolf Schubert, Ivica Grgic, Larisa Vilianovich, Günter Giebing, Tanja Maier, Volkmar Gross, Michael Bader, Cor de Wit, Joachim Hoyer, and Ralf Köhler
Circ. Res. 2006 99: 537-544. [Abstract] [Full Text] [PDF]

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