Dataset Information

Ryanodine Receptor Open Times Are Determined in the Closed State.

ABSTRACT: The ryanodine receptor (RyR) ion channel releases Ca²⁺ from intracellular stores by conducting Ca²⁺ but also by recruiting neighboring RyRs to open, as RyRs are activated by micromolar levels of cytosolic Ca²⁺. Using long single-RyR recordings of the cardiac isoform (RyR2), we conclude that Ca²⁺ binding to the cytosolic face of RyR while the channel is closed determines the distribution of open times. This mechanism explains previous findings that RyR is not activated by its own fluxed Ca²⁺. Our measurements also bolster previous findings that luminal [Ca²⁺] can affect both the cytosolic activation and inactivation sites and that RyR has different gating modes for the same ionic conditions.

SUBMITTER: Fill M

PROVIDER: S-EPMC6170654 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Ryanodine Receptor Open Times Are Determined in the Closed State.

Fill Michael M Gillespie Dirk D

Biophysical journal 20180913 7

The ryanodine receptor (RyR) ion channel releases Ca2+ from intracellular stores by conducting Ca2+ but also by recruiting neighboring RyRs to open, as RyRs are activated by micromolar levels of cytosolic Ca2+. Using long single-RyR recordings of the cardiac isoform (RyR2), we conclude that Ca2+ binding to the cytosolic face of RyR while the channel is closed determines the distribution of open times. This mechanism explains previous findings that RyR ...[more]

PMID: 30220413

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Project description:Introduction: Previous studies have shown significant conditional differences between eyes open, fixated at an image (EO) and eyes closed (EC) in the acquired resting-state functional magnetic resonance imaging (rs-fMRI) data. Aim: We recently showed significant functional network connectivity (FNC) differences between EO and EC across a variety of networks. In this study, we aim at further evaluating differences in dynamic FNC (dFNC) between EO and EC. Materials and Methods: Rs-fMRI were collected from adolescents aged 9-15 years old during both EO and EC conditions, and dFNC was calculated by using the independent component analysis framework. Results: We found that out of five states (clusters), state 1 was observed to be more dominant in the EO condition, whereas state 2 was observed to be more dominant in the EC condition. States 1 and 2 showed significant differences in the mean dwell time based on false discovery rate, and states 1, 2, 3, and 4 differed in the frequency of occurrences. These results are consistent with our previous study of static connectivity in suggesting that EO and EC differences not only are relatively strong but also importantly reveal that these differences vary over time, especially in one particularly transient connectivity pattern. Conclusion: Our results manifest as changes in the proportion of time spent in unique functional connectivity patterns, and they show unique transient functional connectivity patterns in a subset of identified states. Overall, our findings indicate that both static and dynamic rs-fMRI connectivity patterns are strongly impacted by basic conditional differences such as EO and EC. Impact statement Our findings not only suggest that eyes open, fixated at an image (EO) and eyes closed (EC) condition-related resting state functional magnetic resonance imaging differences are relatively strong, but they also reveal an important attribute of these conditions that these differences vary over time, especially in one particularly transient connectivity pattern. Our results manifest as changes in the proportion of time spent in unique functional connectivity patterns, and they show unique transient functional connectivity patterns in a subset of identified states. We believe there is benefit in having the EO/EC as a contrast of interest in future studies, if time allows.

Dataset Information

Ryanodine Receptor Open Times Are Determined in the Closed State.

Publications

Ryanodine Receptor Open Times Are Determined in the Closed State.

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