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The role of the sarcoplasmic reticulum in various types of cardiomyocytes

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Abstract

The relative importance of the sarcoplasmic reticulum (SR) as a source of Ca2+ in the excitation-contraction coupling of mammalian myocytes was tested. Shortening and intracellular Ca2+ transients of electrically paced, isolated,adult rat myocytes were found to be absolutely dependent on the presence of a functional SR and were completely abolished by the SR Ca2+-ATPase inhibitors cyclopiazonic acid and thapsigargin or by the Ca2+-release channel opener ryanodine.Neonatal rat cardiomyocytes, on the other hand, elicited consistent intracellular Ca2+-transients even after complete functional inhibition of the SR. The transients, however, were markedly prolonged. Also isolatedadult guinea pig myocytes maintained the ability to shorten after a complete inhibition of the SR Ca2+-ATPase by either thapsigargin or cyclopiazonic acid. The twitches and the intracellular Ca2+-transients, however, were considerably longer after inhibition of the SR Ca2+-ATPase. Different results were obtained after preincubation of the cells with 10 μM ryanodine to induce emptying of the SR Ca2+ pool. In this case, Ca2+ spikes and twitches were also markedly reduced in size, in addition to being prolonged. When a SR Ca2+-pump inhibitor was added to ryanodine-treated cells, the size of the Ca2+-transients and the capacity of the cells to shorten increased. Ryanodine leaves the activity of the Ca2+-pump of the SR intact and thus leads to an underestimation of the amount of excitatory Ca2+-flowing into the cell.

The results show that, while the significance of the SR in regulating the Ca2+-transients and shortening of cardiomyocytes varies depending on the species and the stage of development, SR function is of paramount importance for the occurrence of rapid twitches.

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Abbreviations

EGTA:

ethylene glycol-bis-(beta amino ethyl ether)N,N,N′,N′ tetraacetic acid

MOPS:

morpholinopropane sulfonic acid

SR:

sarcoplasmic reticulum

BSA:

bovine serum albumin

HEPES:

N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid

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Author notes

  1. Antoni Wrzosek

    Present address: Nencki Institute of Experimental Biology, Warsaw, Poland

Authors and Affiliations

  1. Pharmaceuticals Division, Ciba-Geigy Ltd., 4002, Basel, Switzerland

    Michele Chiesi & Stephan Grueninger

Authors
  1. Michele Chiesi
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  2. Antoni Wrzosek
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  3. Stephan Grueninger
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Chiesi, M., Wrzosek, A. & Grueninger, S. The role of the sarcoplasmic reticulum in various types of cardiomyocytes. Mol Cell Biochem 130, 159–171 (1994). https://doi.org/10.1007/BF01457397

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  • DOI: https://doi.org/10.1007/BF01457397

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