Upregulation of Ca2+ removal in human skeletal muscle: A possible role for Ca2+-dependent priming of mitochondrial ATP synthesis

Werner J.H. Koopman, Michel Renders, Arie Oosterhof, Toin H. Van Kuppevelt, Baziel G.M. Van Engelen, Peter H.G.M. Willems*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

In muscles ATP is required for the powerstroke of the myosin head, the detachment of actin and myosin filaments, and the reuptake of Ca2+ into the sarcoplasmic reticulum. During contraction-relaxation, large amounts of ATP are consumed at the sites of action of the myosin-ATPase and sarcoplasmic reticulum Ca2+-ATPase. The present study addresses the consequences of a reduction in mitochondrial ATP production capacity on sarcoplasmic Ca2+ handling. To this end, myotubes were cultured from patient quadriceps with a biochemically defined decrease in the maximal rate of mitochondrial ATP production and were loaded with indo 1 for imaging of sarcoplasmic Ca2+ changes in real time by confocal microscopy. Myotubes were field-stimulated with 10-ms pulses of 16 V to evoke transient rises in sarcoplasmic Ca2+ concentration ([Ca2+] S). Three single pulses, two pulse trains (1 Hz), and one single pulse were applied in succession to mimic changing workloads. Control myotubes displayed [Ca2+]S transients with an amplitude that was independent of the strength of the stimulus. Intriguingly, the rate of sarcoplasmic Ca2+ removal (CRR) was significantly upregulated during the second and subsequent transients. In myotubes with a reduced mitochondrial ATP production capacity, the amplitude of the [Ca2+]S transients was markedly increased at higher stimulus intensities. Moreover, upregulation of the CRR was significantly decreased compared with control. Taken together, these results are in good agreement with a tight coupling between mitochondrial ATP production and sarcoplasmic Ca2+ handling. Moreover, they support the existence of a relatively long-lasting mitochondrial memory for sarcoplasmic [Ca2+] rises. This memory, which manifested itself as an increase in CRR upon recurrent stimulation, was impaired in patient myotubes with a reduced mitochondrial ATP production capacity.

Original languageEnglish
Pages (from-to)C1263-C1269
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number5 54-5
DOIs
Publication statusPublished - Nov 2003
Externally publishedYes

Keywords

  • Electrical stimulation
  • Indo 1
  • Mitochondrial memory
  • Sarcoplasmic Ca removal
  • Video-rate imaging

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