Identification of Changes in the Functional Profile of the Cardiac Ryanodine Receptor Caused by the Coupled Gating Phenomenon |
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Authors: | Jana Gaburjakova Marta Gaburjakova |
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Institution: | (1) Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34 Bratislava, Slovak Republic; |
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Abstract: | The objective of this work was to identify and further characterize potential changes in the functional profile of the cardiac
ryanodine receptor (RyR2) channel caused by the coupled gating phenomenon. By reconstituting an ion channel into a planar
lipid membrane, we showed that coupled RyR2 channels were activated by cytosolic Ca2+ with similar efficacy and potency as reported for the single RyR2 channel. In contrast, all examined parameters of gating
kinetics were affected by the functional interaction between channels. Ignoring brief closings during main open events, the
average open and closed times were considerably prolonged and the frequency of opening was reduced. Interestingly, when luminal
Ca2+ was used as a charge carrier, Ca2+-activated coupled RyR2 channels did not exhibit a sudden switch from slow to fast gating kinetics at an open probability
of 0.5 as reported for the single RyR2 channel. Regarding flicker gating, the average closed time was significantly shorter
and the frequency of closing was greatly enhanced. Furthermore, in contrast to the single RyR2 channel, both parameters for
coupled channels were independent of cytosolic Ca2+. Selected permeation properties of coupled RyR2 channels were comparable to those found for the single RyR2 channel. The
Ca2+ current amplitude-luminal Ca2+ relationship displayed a simple saturation and the channel selectivity for Ba2+ and Ca2+ ions was similar. Our results suggest that the major targets influenced by coupled gating are likely the gates of individual
RyR2 channels recruited into a functional complex, thus ensuring the correlation of Ca2+ fluxes. |
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