Reduced gain of excitation-contraction coupling in triadin-null myotubes is mediated by the disruption of FKBP12/RyR1 interaction

Jose M. Eltit, John Szpyt, Hongli Li, Paul D. Allen, Claudio F. Perez

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Several studies have suggested that triadin (Tdn) may be a critical component of skeletal EC-coupling. However, using Tdn-null mice we have shown that triadin ablation results in no significant disruption of skeletal EC-coupling. To analyze the role of triadin in EC-coupling signaling here we used whole-cell voltage clamp and simultaneous recording of intracellular Ca2+ release to characterize the retrograde and orthograde signaling between RyR1 and DHPR in cultured myotubes. DHPR Ca2+ currents elicited by depolarization of Wt and Tdn-null myotubes displayed similar current densities and voltage dependence. However, kinetic analysis of the Ca2+ current shows that activation time constant of the slow component was slightly decreased in Tdn-null cells. Voltage-evoked Ca2+ transient of Tdn-null myotubes showed small but significant reduction in peak fluorescence amplitude but no differences in voltage dependence. This difference in Ca2+ amplitude was averted by over-expression of FKBP12.6. Our results show that bi-directional signaling between DHPR and RyR1 is preserved nearly intact in Tdn-null myotubes and that the effect of triadin ablation on Ca2+ transients appears to be secondary to the reduced FKBP12 binding capacity of RyR1 in Tdn-null myotubes. These data suggest that skeletal triadins do not play a direct role in skeletal EC-coupling.

Original languageEnglish (US)
Pages (from-to)128-135
Number of pages8
JournalCell Calcium
Volume49
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • Calcium imaging
  • Myotubes
  • Orthograde signal
  • Patch clamp
  • Retrograde signal

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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