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(Circulation Research. 2007;100:5.)
© 2007 American Heart Association, Inc.

Editorials

The Cardiac Sarcoplasmic Reticulum

Filled With Ca²⁺ and Surprises

Ernst Niggli

From the Department of Physiology, University of Bern, Switzerland.

Correspondence to Ernst Niggli, Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland. E-mail niggli@pyl.unibe.ch

Key Words: Ca²⁺ transients • calcium signaling • ryanodine receptor • sarcoplasmic reticulum

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

Ca²⁺-induced Ca²⁺ release (CICR) from the sarcoplasmic reticulum (SR) is the cornerstone of cardiac excitation-contraction coupling and Ca²⁺ signaling.^1,2 However, as an amplification mechanism exhibiting a high degree of positive feed-back, it has to be kept in check by inhibitory systems to prevent spontaneous oscillatory Ca²⁺ releases which could possibly trigger cardiac arrhythmias. Local control theory provides us with an initial frame-work to understand how this could be accomplished.³ Mutually independent Ca²⁺ signaling events (Ca²⁺ sparks⁴) generate the necessary amplification locally without spreading to neighboring Ca²⁺ release sites, whereas the normal signal transduction from L-type Ca²⁺ channels to the SR occurs within the microdomain of the dyadic cleft, well isolated from the bulk of the cytosol. Uncoupling between neighboring Ca²⁺ spark sites thus ensures the reliability of the CICR system and occurs by virtue of steep concentration gradients away from the microdomain of Ca²⁺ release, and by means of the relative insensitivity of the SR Ca²⁺ release channels (ryanodine receptors [RyRs]) toward cytosolic Ca²⁺ triggers.⁵ This uncoupling by local control also underlies the observation that Ca²⁺ sparks occurring spontaneously remain localized and do not initiate a chain reaction of Ca²⁺ sparks traveling along the entire myocyte as a Ca²⁺ wave.

However, this system can also become unstable and CICR is capable to override local control and to trigger oscillatory Ca²⁺ signals in cardiomyocytes, particularly under pathophysiological conditions. Waves of contractions traveling along isolated cardiomyocytes have been discovered and the underlying Ca²⁺ waves have been imaged with fluorescent Ca²⁺ . . . [Full Text of this Article]

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