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

Sankaranarayanan, R, Li, Y, Greensmith, DJ ORCID:, Eisner, DA and Venetucci, L 2016, 'Biphasic decay of the Ca transient results from increased sarcoplasmic reticulum Ca leak' , The Journal of Physiology, 594 (3) , pp. 611-623.

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In heart failure, a 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 characterised the effects of two forms of Ca leak (Ca-sensitising and non-sensitising) on calcium cycling and compared with those of SERCA inhibition. We measured [Ca2+]i with fluo-3 in voltage-clamped rat ventricular myocytes. Increasing SR leak with either caffeine (to sensitise the RyR to Ca activation) or ryanodine (non-sensitising) had similar effects to SERCA inhibition: decreased systolic [Ca2+]i, increased diastolic [Ca2+]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 decay of Ca waves, biphasic or monophasic, occurs.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: The Journal of Physiology
Publisher: The Physiological Society
ISSN: 0022-3751
Related URLs:
Funders: The British Heart Foundation
Depositing User: D Greensmith
Date Deposited: 03 Feb 2016 09:19
Last Modified: 15 Feb 2022 20:17

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