Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak.

Rajiv Sankaranarayanan, Yatong Li, David J Greensmith, David A Eisner, Luigi Venetucci

Research output: Contribution to journalArticlepeer-review


In heart failure reduction in Ca transient amplitude and contractile dysfunction can by caused by Ca leak through the sarcoplasmic reticulum (SR) Ca channel (Ryanodine Receptor, RyR) and/or decreased activity of the SR Ca ATPase (SERCA). We have characterized the effects of two forms of Ca leak (Ca-sensitizing and non-sensitizing) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca(2+) ]i with fluo-3 in voltage-clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitize the RyR to Ca activation) or ryanodine (non-sensitizing) had similar effects to SERCA inhibition: decreased systolic [Ca(2+) ]i , increased diastolic [Ca(2+) ]i and slowed decay. However, in the presence of isoproterenol, leak produced a biphasic decay of the Ca transient in the majority of cells while SERCA inhibition produced monophasic decay. Tetracaine reversed the effects of caffeine but not of ryanodine. When caffeine (1 mmol l(-1) ) was added to a cell which displayed Ca waves, the wave frequency initially increased before waves disappeared and biphasic decay developed. Eventually (at higher caffeine concentrations), the biphasic decay was replaced by slow decay. We conclude that, in the presence of adrenergic stimulation, Ca leak can produce biphasic decay; the slow phase results from the leak opposing Ca uptake by SERCA. The degree of leak determines whether Ca waves, biphasic or monophasic decay occur. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)611-623
Number of pages13
JournalThe Journal of Physiology
Issue number3
Early online date5 Nov 2015
Publication statusE-pub ahead of print - 5 Nov 2015


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