Different interactions of cardiac and skeletal muscle ryanodine receptors with FK-506 binding protein isoforms.
In the present study, we compare functional consequences of dissociation and reconstitution of binding proteins FKBP12 and FKBP12.6 with ryanodine receptors from cardiac (RyR2) and skeletal muscle (RyR1). The skeletal muscle RyR1 channel became activated on 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 FKBP12.6 had no effect on channel activity of FKBP12.6-depleted cardiac RyR2, although 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.
Barg
S
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Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Copello
J A
JA
Fleischer
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006360:Heat-Shock Proteins / Q000378:metabolism* / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
D015220:Calcium Channels; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007473:Ion Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D000255:Adenosine Triphosphate; D022021:Tacrolimus Binding Proteins; D008274:Magnesium; D002118:Calcium