SINGLE-CHANNEL ACTIVITY OF THE RYANODINE RECEPTOR CALCIUM-RELEASE CHANNEL IS MODULATED BY FK-506

The immunosuppressant drug FK-506 (3-20 mu M) increased the open proba bility of ryanodine receptor calcium release channels, formed by incor poration of terminal cisternae vesicles from rabbit skeletal muscle in to lipid bilayers, with cis (cytoplasmic) calcium concentrations betwe en 10(-7) M and 10(-3) M. FK-506 increased mean current and channel op en time and induced long sojourns at subconductance levels that were b etween 28% and 38% of the maximum conductance and were distinct from t he ryanodine-induced subconductance level at about 45% of the maximum conductance. FK-506 relieved the Ca2+ inactivation of the ryanodine re ceptor seen at 10(-3) M Ca2+. The results are consistent with FK-506 r emoval of FK-506 binding protein from the ryanodine receptor [15].