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PMID: 8599646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rectification of skeletal muscle ryanodine receptor mediated by FK506 binding protein.

Biophysical journal ·Vol. 69 ·No. 6 ·1995-12-00 ·Pages 2398-404

Ma J, Bhat MB, Zhao J

Abstract

The cytosolic receptor for immunosuppressant drugs, FK506 binding protein (FKBP12), maintains a tight association with ryanodine receptors of sarcoplasmic reticulum (SR) membrane in skeletal muscle. The interaction between FKBP12 and ryanodine receptors resulted in distinct rectification of the Ca release channel. The endogenous FKBP-bound Ca release channel conducted current unidirectionally from SR lumen to myoplasm; in the opposite direction, the channel deactivated with fast kinetics. The binding of FKBP12 is likely to alter subunit interactions within the ryanodine receptor complex, as revealed by changes in conductance states of the channel. Both on- and off-rates of FKBP12 binding to the ryanodine receptor showed clear dependence on the membrane potential, suggesting that the binding sites of FKBP12 reside in or near the conduction pore of the Ca release channel. Rectification of the Ca release channel would prevent counter-current flow during the rapid release of Ca from SR membrane, and thus may serve as a negative feedback mechanism that participates in the process of muscle excitation-contraction coupling.

MeSH Terms
Animals Calcium/metabolism Calcium Channels/physiology Carrier Proteins/physiology DNA-Binding Proteins/physiology Electric Conductivity Electrophysiology/instrumentation,methods Heat-Shock Proteins/physiology Ion Channel Gating Kinetics Lipid Bilayers Membrane Potentials Muscle Proteins/physiology Muscle, Skeletal/physiology Protein Binding Rabbits Ryanodine Receptor Calcium Release Channel Sarcoplasmic Reticulum/physiology Tacrolimus/metabolism Tacrolimus Binding Proteins Time Factors
Chemicals
Calcium Channels Carrier Proteins DNA-Binding Proteins Heat-Shock Proteins Lipid Bilayers Muscle Proteins Ryanodine Receptor Calcium Release Channel Tacrolimus Binding Proteins Calcium Tacrolimus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ma J
Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA. jxm63@po.cwru.edu
Bhat M B
Zhao J
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
Published
1995-12-00
Pages
2398-404
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1236477
Subset
IM
Grants
NIAMS NIH HHS · AR42057 · United States
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