Single channel activity of the ryanodine receptor calcium release channel is modulated by FK-506

FEBS Lett. 1994 Oct 3;352(3):369-74. doi: 10.1016/0014-5793(94)01001-3.

Abstract

The immunosuppressant drug FK-506 (3-20 microM) increased the open probability of ryanodine receptor calcium release channels, formed by incorporation of terminal cisternae vesicles from rabbit skeletal muscle into lipid bilayers, with cis (cytoplasmic) calcium concentrations between 10(-7) M and 10(-3) M. FK-506 increased mean current and channel open time and induced long sojourns at subconductance levels that were between 28% and 38% of the maximum conductance and were distinct from the ryanodine-induced subconductance level at about 45% of the maximum conductance. FK-506 relieved the Ca2+ inactivation of the ryanodine receptor seen at 10(-3) M Ca2+. The results are consistent with FK-506 removal of FK-506 binding protein from the ryanodine receptor.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Cytoplasm / metabolism
  • Electric Conductivity
  • Ion Channel Gating
  • Kinetics
  • Lipid Bilayers
  • Membrane Potentials / drug effects
  • Muscle Proteins / drug effects
  • Muscle Proteins / physiology*
  • Muscles / metabolism
  • Rabbits
  • Ryanodine / pharmacology*
  • Ryanodine Receptor Calcium Release Channel
  • Tacrolimus / pharmacology*
  • Time Factors

Substances

  • Calcium Channels
  • Lipid Bilayers
  • Muscle Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Ryanodine
  • Calcium
  • Tacrolimus