Cytosolic Ca(2+) buffering determines the intra-SR Ca(2+) concentration at which cardiac Ca(2+) sparks terminate Journal Article

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Authors: Bovo, E; Mazurek, S. R.; Fill, M.; Zima, A. V.
Article Title: Cytosolic Ca(2+) buffering determines the intra-SR Ca(2+) concentration at which cardiac Ca(2+) sparks terminate
Abstract: Single ryanodine receptor (RyR) Ca(2+) flux amplitude (iCa-RyR) decreases as intra-sarcoplasmic reticulum (SR) Ca(2+) levels fall during a cardiac Ca(2+) spark. Since iCa-RyR drives the inter-RyR Ca(2+)-induced Ca(2+) release (CICR) that underlies the spark, decreasing iCa-RyR may contribute to spark termination because RyRs that spontaneously close may stay closed. To test this possibility, we simultaneously measured local cytosolic and intra-SR ([Ca(2+)]cyto and [Ca(2+)]SR) during Ca(2+) sparks in permeabilized rabbit ventricular myocytes. Local cytosolic or intra-SR Ca(2+) dynamics were manipulated using Ca(2+) buffers. Buffer manipulations applied in cells had no effect on individual RyR channels reconstituted in planar lipid bilayers. Presence of a fast cytosolic Ca(2+) buffer (BAPTA) significantly suppressed Ca(2+) spark activity and sparks terminated earlier at a higher than usual [Ca(2+)]SR level ( approximately 80% vs. approximately 62%). When cytosolic Ca(2+) buffer power was reduced (i.e. cytosolic EGTA level decreased), sparks terminated later and at a lower than usual [Ca(2+)]SR level ( approximately 45% vs. approximately 62%). When intra-SR Ca(2+) buffer power was increased, sparks also terminated later and at a lower than usual [Ca(2+)]SR ( approximately 48% vs. approximately 62%). These results suggest that cytosolic local control of inter-RyR CICR by iCa-RyR plays a substantial role during the spark termination process. Thus, alterations in local cytosolic Ca(2+) handling dynamics in the dyadic cleft (Ca(2+) buffering, extrusion, etc.) likely influence Ca(2+) spark termination.
Journal Title: Cell calcium
Volume: 58
Issue: 3
ISSN: 1532-1991; 0143-4160
Publisher: Unknown  
Journal Place: Netherlands
Date Published: 2015
Start Page: 246
End Page: 253
Language: eng
DOI/URL:

10.1016/j.ceca.2015.06.002
Notes: LR: 20150827; CI: Copyright (c) 2015; GR: R01 AR054098/AR/NIAMS NIH HHS/United States; GR: R01 HL057832/HL/NHLBI NIH HHS/United States; JID: 8006226; NIHMS705372; OID: NLM: NIHMS705372 [Available on 09/01/16]; OID: NLM: PMC4550446 [Available on 09/01/16]; OTO: NOTNLM; PMCR: 2016/09/01 00:00; 2015/04/10 [received]; 2015/06/04 [revised]; 2015/06/06 [accepted]; 2015/06/10 [aheadofprint]; ppublish