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(Circulation Research. 2007;101:436.)
© 2007 American Heart Association, Inc.

Editorials

Stoking Up BK_Ca Channels in Hemorrhagic Shock

Which Channel Subunit Is Really Fueling the Fire?

Lucie H. Clapp, Nelson N. Orie

From the BHF Laboratories, Department of Medicine, UCL, London, UK.

Correspondence to Professor Lucie Clapp, BHF Laboratories, Department of Medicine, UCL, 4th floor Rayne Building, 5 University Street, London WC1E 6JF. E-mail l.clapp@ucl.ac.uk

See related article, pages 493–502

Key Words: potassium channels • shock • hypotension • vascular hyporeactivity • Ca²⁺ sparks

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

	Introduction

 
Large conductance calcium-activated potassium channels (BK_Ca) are abundantly expressed in smooth muscle cells (SMCs) lining the blood vessel wall. They are composed of an -subunit (Slo) and a modulatory ß1-subunit, which serves to maintain the normal high voltage- and Ca²⁺-sensitivity of the pore-forming -subunit (reviewed in^1,2). In the vasculature, BK_Ca operate by limiting Ca²⁺ entry and arterial contraction by repolarizing SMCs and closing voltage-dependent Ca²⁺ channels previously opened by pressure or vasoconstrictor agents.¹ BK_Ca can also mediate cellular hyperpolarization and vasorelaxation as a result of spontaneous transient outward currents (STOCs) activated by the localized release of micromolar concentrations of Ca²⁺ (Ca²⁺ sparks) from ryanodine receptors located in the sarcoplasmic reticulum (SR).¹ Moreover, increased frequency of Ca²⁺ sparks may underlie activation of BK_Ca by endogenous vasodilators,¹ though other mechanisms undoubtedly contribute.^2,3

Genetic experiments also highlight BK_Ca as important regulators of vascular tone and blood pressure. Deletion of the -subunit in mice results in membrane depolarization, a complete lack of STOCs, and attenuates cGMP relaxation in isolated blood vessels.⁴ On the other hand, deletion of ß1 impairs the coupling of Ca²⁺ sparks to the activation of hyperpolarizing BK_Ca currents and enhances agonist-induced vasoconstriction without affecting nitric oxide (NO) mediated vasorelaxation.³ Knockout of both genes leads to systemic hypertension, though in BK_Ca ß1–null mice this is more pronounced^3,4 suggesting physical interactions of the ß1-subunit with other proteins, possibly other ion-conducting pores.⁵ Moreover, depending on the hypertensive model, ß1-subunit expression can either increase^2,6 or decrease.⁷ The latter might argue that ß1 . . . [Full Text of this Article]

Related Article:

Hypersensitivity of BK_Ca to Ca²⁺ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock

Guiling Zhao, Yan Zhao, Bingxing Pan, Jie Liu, Xuliang Huang, Xiuqin Zhang, Chunmei Cao, Ning Hou, Caihong Wu, Ke-seng Zhao, and Heping Cheng
Circ. Res. 2007 101: 493-502. [Abstract] [Full Text] [PDF]

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