Relative importance of SR load and cytoplasmic calcium concentration in the genesis of aftercontractions in cardiac myocytes

doi:10.1016/S0008-6363(00)00147-4

Cardiovascular Research 2000 47(4):769-777; doi:10.1016/S0008-6363(00)00147-4
© 2000 by European Society of Cardiology

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Relative importance of SR load and cytoplasmic calcium concentration in the genesis of aftercontractions in cardiac myocytes

Robin M. Egdell^*, Ayesha I. De Souza and Kenneth T. Macleod

Cardiac Medicine, Imperial College School of Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK

^* Corresponding author. Tel.: +44-171-352-8121; fax: +44-171-351-8145 r.egdell{at}hotmail.com

Objective: To determine whether calcium overload of the sarcoplasmicreticulum underlies drive train-induced aftercontractions incardiac myocytes. Methods: Sarcoplasmic reticulum calcium contentswere measured immediately prior to drive train-induced aftercontractionsin isolated guinea pig cardiac myocytes, using caffeine applicationunder voltage clamp conditions. Cell shortening during caffeineexposure and cell shortening during the final stimulated beatof the drive train and the delay between caffeine exposure andthe onset of inward current were also used as indirect measuresof sarcoplasmic reticulum load. Results: At the threshold foraftercontractions, all four measures of sarcoplasmic reticulumload showed interruption of the positive relationship betweenstimulation frequency and sarcoplasmic reticulum content, thesarcoplasmic reticulum being no more loaded prior to an aftercontractionthan following subthreshold drive trains. Intracellular calciumconcentration, estimated with the calcium-sensitive dye indo-1,was higher in cells showing aftercontractions than those not.Conclusions: We conclude that calcium overload of the sarcoplasmicreticulum does not underlie spontaneous calcium release in thissituation and the primary trigger for spontaneous release mayinstead be raised cytoplasmic calcium concentration.

KEYWORDS Arrhythmia (mechanisms); Calcium (cellular); e–c coupling; Myocytes; SR (function)

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