Different interactions of cardiac and skeletal muscle ryanodine
receptors with fk506 binding protein isoforms.
Barg, Sebastian, Julio A. Copello, and Sidney Fleischer.
Department of Molecular Biology, Vanderbilt University, Nashville
TN 37235
APStracts 3:0418C, 1996.
In the present study, we compare functional consequences of
dissociation and reconstitution of FKBP12 and FKBP12.6 with ryanodine
receptors from cardiac (RyR2) and skeletal muscle (RyR1). The
skeletal muscle RyR1 channel becomes activated upon removal of
endogenously bound FKBP12, consistent with previous reports. Both
FKBP12 and FKBP12.6 rebind to FKBP depleted RyR1 and restore its
quiescent channel behavior by altering ligand sensitivity, as studied
by single channel recordings in planar lipid bilayers, and
macroscopic behavior of the channels (ryanodine binding and net
energized Ca2+ uptake). By contrast, removal of FKBP12.6 from the
cardiac RyR2 did not modulate the function of the channel using the
same types of assays as for RyR1. FKBP12 or 12.6 have no effect on
channel activity of FKBP12.6 depleted cardiac RyR2, albeit FKBP12.6
rebinds. Our studies reveal important differences between the two
ryanodine receptor isoforms with respect to their functional
interaction with FKBP12 and FKBP12.6.
Received 23 September 1996; accepted in final form 16 December
1996.
APS Manuscript Number C554-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996