JCI - Calmodulin kinase II–mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice

Calmodulin kinase II–mediated sarcoplasmic reticulum Ca²⁺ leak promotes atrial fibrillation in mice

Mihail G. Chelu, Satyam Sarma, Subeena Sood, Sufen Wang, Ralph J. van Oort, Darlene G. Skapura, Na Li, Marco Santonastasi, Frank Ulrich Müller, Wilhelm Schmitz, Ulrich Schotten, Mark E. Anderson, Miguel Valderrábano, Dobromir Dobrev, Xander H.T. Wehrens

Published in Volume 119, Issue 7

J Clin Invest. 2009; 119(7):1940–1951 doi:10.1172/JCI37059

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Figure 4

Pharmacological inhibition of CaMKII reverses enhanced SR Ca²⁺ leak in Ryr2^R176Q/+ atrial myocytes.

Representative [Ca²⁺]_i recordings obtained from fluo-4 AM–loaded atrial myocytes from WT (A) and Ryr2^R176Q/+ (B) mice during 1 Hz pacing in 1.8 mM Ca²⁺ (left), followed by a rapid switch to Tyrode solution containing 0 Na⁺, 0 Ca²⁺, and tetracaine (TTC) (1 mmol/l). Tetracaine was washed out 30 seconds later, and SR Ca²⁺ content was measured by changing superfusate to 10 mmol/l caffeine in 0 Na⁺, 0 Ca²⁺ Tyrode solution. SR Ca²⁺ leak was measured as shown in red and related to SR Ca²⁺ content. (C) Bar graph represents quantification of SR Ca²⁺ leak normalized to SR Ca²⁺ content in the presence and absence of KN-93 in WT and Ryr2^R176Q/+ atrial myocytes. *P < 0.05. Numbers in bars indicate numbers of myocytes tested.