Abstract
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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