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(Circulation Research. 2005;96:607.)
© 2005 American Heart Association, Inc.

Editorials

Triadin

The New Player on Excitation-Contraction Coupling Block

Martin Morad, Lars Cleemann, Björn C. Knollmann

From the Department of Pharmacology, Georgetown University, Washington, DC.

Correspondence to Martin Morad, Georgetown University, Dept. of Pharmacology, 3900 Reservoir Road, NW, Washington DC, 20057. E-mail moradm@georgetown.edu

See related article, pages 651–658

Key Words: triadin overexpression • cardiac Ca²⁺ signaling • cardiac EC coupling • ryanodine receptors • calsequestrin • arrythmia

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

	Introduction

 
The Ca²⁺ movements that control many cellular functions, including contraction of striated and smooth muscle cells and vesicular secretion from endocrine cells and nerve terminals, are increasingly recognized to involve macromolecular Ca²⁺-signaling complexes that, in addition to the key Ca²⁺-transporting proteins, include large numbers of associated proteins that provide a variety of regulatory, structural and Ca²⁺-sensing/buffering functions. The importance of working out the subtle interactions within these macromolecular complexes is underscored by the genetic diseases that have been associated with mutations of their constituent proteins.

In this issue, Terentyev et al¹ use a spectrum of molecular and electrophysiological techniques to demonstrate that triadin (TRD) plays an unexpectedly important role in regulating the ryanodine receptors (RyRs), found primarily in dyadic junctions of cardiac sarcoplasmic reticulum (SR; Figure). It has been previously suggested that TRD and junctin are integral membrane proteins of the junctional SR, and serve as linker proteins from the SR Ca release channel (RyR) to calsequestrin (CSQ) complexes, the major Ca²⁺-buffer in the lumen of the SR (Figure).² The large (4500 aa) cytoplasmic domain of RyR appears to have multiple binding sites for an ever-growing list of proteins that includes: calmodulin, PKA, FKBP 12.6.³ The major findings of the present communication are that overexpression of TRD leads to 3-fold increase in open probability of RyRs in bilayers, a 60% increase in spontaneous spark frequency with only minor decreases in spark amplitude (10%) and SR Ca²⁺ content (30%), as well . . . [Full Text of this Article]

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