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The Role of Dyadic Organization in Regulation of Sarcoplasmic Reticulum Ca(2+) Handling during Rest in Rabbit Ventricular Myocytes Journal Article
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| Authors: | Bovo, E; de Tombe, P. P.; Zima, A. V. |
| Article Title: | The Role of Dyadic Organization in Regulation of Sarcoplasmic Reticulum Ca(2+) Handling during Rest in Rabbit Ventricular Myocytes |
| Abstract: | The dyadic organization of ventricular myocytes ensures synchronized activation of sarcoplasmic reticulum (SR) Ca(2+) release during systole. However, it remains obscure how the dyadic organization affects SR Ca(2+) handling during diastole. By measuring intraluminal SR Ca(2+) ([Ca(2+)]SR) decline during rest in rabbit ventricular myocytes, we found that approximately 76% of leaked SR Ca(2+) is extruded from the cytosol and only approximately 24% is pumped back into the SR. Thus, the majority of Ca(2+) that leaks from the SR is removed from the cytosol before it can be sequestered back into the SR by the SR Ca(2+)-ATPase (SERCA). Detubulation decreased [Ca(2+)]SR decline during rest, thus making the leaked SR Ca(2+) more accessible for SERCA. These results suggest that Ca(2+) extrusion systems are localized in T-tubules. Inhibition of Na(+)-Ca(2+) exchanger (NCX) slowed [Ca(2+)]SR decline during rest by threefold, however did not prevent it. Depolarization of mitochondrial membrane potential during NCX inhibition completely prevented the rest-dependent [Ca(2+)]SR decline. Despite a significant SR Ca(2+) leak, Ca(2+) sparks were very rare events in control conditions. NCX inhibition or detubulation increased Ca(2+) spark activity independent of SR Ca(2+) load. Overall, these results indicate that during rest NCX effectively competes with SERCA for cytosolic Ca(2+) that leaks from the SR. This can be explained if the majority of SR Ca(2+) leak occurs through ryanodine receptors in the junctional SR that are located closely to NCX in the dyadic cleft. Such control of the dyadic [Ca(2+)] by NCX play a critical role in suppressing Ca(2+) sparks during rest. |
| Journal Title: | Biophysical journal |
| Volume: | 106 |
| Issue: | 9 |
| ISSN: | 1542-0086; 0006-3495 |
| Publisher: | Unknown |
| Journal Place: | United States |
| Date Published: | 2014 |
| Start Page: | 1902 |
| End Page: | 1909 |
| Language: | eng |
| DOI/URL: | |
| Notes: | CI: Copyright (c) 2014; JID: 0370626; 2013/11/04 [received]; 2014/02/24 [revised]; 2014/03/25 [accepted]; ppublish |
