Coupled gating between cardiac calcium release channels (ryanodine receptors).
Excitation-contraction coupling in heart muscle requires the activation of Ca(2+)-release channels/type 2 ryanodine receptors (RyR2s) by Ca(2+) influx. RyR2s are arranged on the sarcoplasmic reticular membrane in closely packed arrays such that their large cytoplasmic domains contact one another. We now show that multiple RyR2s can be isolated under conditions such that they remain physically coupled to one another. When these coupled channels are examined in planar lipid bilayers, multiple channels exhibit simultaneous gating, termed "coupled gating." Removal of the regulatory subunit, the FK506 binding protein (FKBP12.6), functionally but not physically uncouples multiple RyR2 channels. Coupled gating between RyR2 channels may be an important regulatory mechanism in excitation-contraction coupling as well as in other signaling pathways involving intracellular Ca(2+) release.
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Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Gaburjakova
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Gaburjakova
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M
Henrikson
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C
Ondrias
K
K
Marks
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D000818:Animals; D001464:Barium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D004396:Coloring Agents / Q000494:pharmacology; D004285:Dogs; D015151:Immunoblotting; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D015636:Magnesium Chloride / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000737:chemistry; D020123:Sirolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
D004396:Coloring Agents; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D019837:Ryanodine Receptor Calcium Release Channel; D015636:Magnesium Chloride; D012430:Ruthenium Red; D012433:Ryanodine; D001464:Barium; D002110:Caffeine; D022021:Tacrolimus Binding Proteins; C403484:tacrolimus binding protein 1B; D020123:Sirolimus