This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ramirez-Correa, G. A. Articles by Murphy, A. M. Search for Related Content PubMed PubMed Citation Articles by Ramirez-Correa, G. A. Articles by Murphy, A. M. Related Collections Related Article

(Circulation Research. 2007;101:326.)
© 2007 American Heart Association, Inc.

Editorials

Is Phospholamban or Troponin I the "Prima Donna" in β-Adrenergic Induced Lusitropy?

Genaro A. Ramirez-Correa, Anne M. Murphy

From the Department of Pediatrics, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore Md.

Correspondence to Anne M. Murphy, Department of Pediatrics, Division of Cardiology, Johns Hopkins University School of Medicine, Ross Building 1144, 720 Rutland Avenue, Baltimore MD 21205. E-mail murphy@jhmi.edu

See related articles, pages 377–386

Key Words: troponin • phospholamban • adrenergic stimulation

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

In normal myocardium, acute β-adrenergic stimulation augments both systolic and diastolic performance via protein kinase A (PKA)–mediated phosphorylation of key proteins governing Ca²⁺ handling and the contractile machinery. Twenty-five years ago Kranias and Solaro identified troponin I (TnI) and phospholamban (PLN) as the 2 major cardiac proteins which were nearly simultaneously phosphorylated by β-adrenergic stimulation of the beating heart in synchrony with the agonist effect of augmenting contractility (inotropy) and rate of relaxation (lusitropy).¹ Numerous subsequent studies have mechanistically examined the role of these proteins in inotropy and lusitropy. It is well established that enhanced Ca²⁺ availability during systole is the major, though perhaps not the only, driver of enhanced inotropy with β- adrenergic stimulation.^2–4 The effect on Ca²⁺ dynamics is primarily mediated by phosphorylation of PLN, though increased ionic current through the L-type calcium channel contributes to Ca²⁺ loading. When PLN is phosphorylated by PKA, the "brake" imposed by PLN on sarcoplasmic reticulum (SR) Ca²⁺ ATPase is relieved, resulting in an increase in the activity of the latter that leads to a faster sequestration of Ca²⁺ into the SR, enhancing cardiac relaxation and re-loading the SR with Ca²⁺ to increase Ca²⁺ release in subsequent beats. Yet, PLN phosphorylation by PKA is not the sole mechanism implicated in enhancing relaxation. In particular, phosphorylation of TnI by PKA has long been proposed to have a role in diastole because it desensitizes the myofilament to Ca²⁺, increases the off rate of Ca²⁺ from troponin, and speeds cross-bridge cycling (reviewed in⁵), . . . [Full Text of this Article]

Related Article:

Cardiac Transgenic and Gene Transfer Strategies Converge to Support an Important Role for Troponin I in Regulating Relaxation in Cardiac Myocytes

So-ichiro Yasuda, Pierre Coutu, Sakthivel Sadayappan, Jeffrey Robbins, and Joseph M. Metzger
Circ. Res. 2007 101: 377-386. [Abstract] [Full Text] [PDF]