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

Cell Calcium. 2011 Feb;49(2):128-35. doi: 10.1016/j.ceca.2011.01.005.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cells, Cultured
  • Excitation Contraction Coupling / physiology*
  • Mice
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics
  • Muscle Proteins / physiology*
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Signal Transduction
  • Tacrolimus Binding Protein 1A / metabolism*

Substances

  • CACNA1S protein, mouse
  • Calcium Channels, L-Type
  • Carrier Proteins
  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • triadin
  • Tacrolimus Binding Protein 1A
  • Calcium