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(Circulation Research. 2005;97:507.)
© 2005 American Heart Association, Inc.

Editorials

The Enigma of ß₂-Adrenergic Receptor G_i Signaling in the Heart

The Good, the Bad, and the Ugly

Weizhong Zhu, Xiaokun Zeng, Ming Zheng, Rui-Ping Xiao

From the Laboratory of Cardiovascular Science (W.Z., X.Z., R.-P.X.), National Institute of Aging, National Institutes of Health, Baltimore, Md; and The Institute of Molecular Medicine (M.Z., R.-P.X.), Peking University, Beijing, China.

Correspondence to Rui-Ping Xiao, MD, PhD, Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224. E-mail xiaor@grc.nia.nih.gov

See related article, pages 566–573

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

	Introduction

 
Four decades ago, it was thought that the cardiac ß-adrenergic receptor (AR) was ß₁AR, the vascular/bronchial counterpart was ß₂AR, and that ß₂AR was either nonexistent or nonfunctional in myocardium.¹ In the heart, stimulation of ß₁AR leads to PKA-dependent phosphorylation of a set of Ca²⁺ regulatory proteins, including sarcolemmal L-type Ca²⁺ channels, sarcoplasmic reticulum (SR) Ca²⁺-release channels (ryanodine receptors), SR Ca²⁺-ATPase (SERCA) and its regulator phospholamban (PLB), and some myofilament proteins, resulting in positive inotropic, lusitropic, and chronotropic effects. However, over the past decade, compelling evidence has shown that the ß₂AR subtype is expressed in the heart and its signaling and functionalities markedly differ from those evoked by the closely related ßAR subtype, the ß₁AR. Unlike ß₁AR, ß₂AR couples dually to G_s and G_i proteins; the ß₂AR-G_i signaling pathway plays a crucial role in cardioprotection against apoptotic death of myocytes in culture and in vivo (the "good"), while attenuating the ß₂AR-G_s-mediated inotropic response (the "bad") (Figure).² Now, in the current issue of Circulation Research, He et al revealed one "ugly" facet of the ß₂AR-G_i signaling in a canine heart failure model.³ They demonstrated that in the failing heart, activation of ß₂AR dampens the ability of ß₁AR, the primary cardiac subtype, to stimulate I_Ca,L, thus resulting in an overall dysfunction of ßAR inotropic response in the failing heart (Figure).³ Specifically, the effect of ßAR stimulation with a nonselective agonist, isoproterenol . . . [Full Text of this Article]

Related Article:

Crosstalk of ß-Adrenergic Receptor Subtypes Through G_i Blunts ß-Adrenergic Stimulation of L-Type Ca²⁺ Channels in Canine Heart Failure

Jia-Qiang He, Ravi C. Balijepalli, Robert A. Haworth, and Timothy J. Kamp
Circ. Res. 2005 97: 566-573. [Abstract] [Full Text] [PDF]

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