Published online before print June 22, 2006, doi: 10.1161/01.RES.0000233386.02708.72
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Submitted on April 19, 2006
Revised on May 31, 2006
Accepted on June 13, 2006
Sarcoplasmic Reticulum and Nuclear Envelope Are One Highly Interconnected Ca2+ Store Throughout Cardiac Myocyte
Xu Wu and Donald M. Bers *
From the Department of Physiology, Loyola University Chicago, Maywood, Ill.
* To whom correspondence should be addressed. E-mail: dbers{at}lumc.edu.
Previous ventricular myocyte studies indicated that ryanodine receptors (RyRs) are in the sarcoplasmic reticulum (SR) and are critical in excitation-contraction coupling, whereas the inositol trisphosphate (InsP3) receptors are separately localized on the nuclear envelope (NucEn) and involved in nuclear Ca2+ signaling. Here, we find that both caffeine and InsP3 receptor agonists deplete free [Ca2+] inside both SR and NucEn. Fluorescence recovery after photobleach (FRAP) was measured using the low-affinity Ca2+ indicator Fluo-5N trapped inside the SR and NucEn (where its fluorescence is high because [Ca2+] is 
1 mmol/L). After Fluo-5N photobleach in 1 end of the cell, FRAP occurred, accompanied by fluorescence decline in the unbleached end with similar time constants (
2 minutes) until fluorescence regained spatial uniformity. Notably, SR and NucEn fluorescence recovered simultaneously in the bleached end. Ca2+ diffusion inside the SR-NucEn was also measured. SR Ca2+-ATPase was completely blocked but without acute SR Ca2+ depletion. Then caffeine was applied locally to 1 end of the myocyte. In the caffeine-exposed end, free SR [Ca2+] ([Ca2+]SR) declined abruptly and recovered partially (=20 to 30 seconds). In the noncaffeine end, [Ca2+]SR gradually declined with a similar , until [Ca2+]SR throughout the cell equalized. We conclude that the SR and NucEn lumen are extensively interconnected throughout the myocyte. Apparent intrastore diffusion coefficients of Fluo-5N and Ca2+ were estimated (8 µm2 sec-1 and 60 µm2 sec-1). This rapid luminal communication may maintain homogeneously high luminal [Ca2+], ensuring a robust and uniform driving force for local Ca2+ release events from either SR or NucEn.
Key words: sarcoplasmic reticulum • nuclear envelope (NucEn) • fluorescence recovery after photobleach (FRAP) • caffeine
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