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Updated: Aug 17, 2026
Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Kinetics of cardiac RyR channel gating studied at high temporal resolution
M Dura1, I Zahradník, A Zahradníková
1Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovak Republic.
Insights
Ryanodine receptors (RyRs) require multiple calcium ions to open. High-resolution measurements reveal three closed times in RyR activity, supporting this multi-ion binding model.
Area of Science:
- Biophysics
- Molecular Biology
- Cardiovascular Research
Background:
- Ryanodine receptors (RyRs) are critical calcium channels in muscle cells.
- Previous studies suggested RyRs have multiple calcium binding sites, but steady-state activity showed only two closed times.
- Dynamic measurements indicated RyR activation involves a high open probability (H-mode) dependent on calcium concentration.
Purpose of the Study:
- To investigate the steady-state activity of single cardiac RyRs with high temporal resolution.
- To compare experimental data with simulations from a previously established RyR gating model.
- To determine if multiple calcium ions are necessary for RyR activation.
Main Methods:
- Recorded steady-state activity of single cardiac ryanodine receptors (RyRs) at 10 kHz resolution.
- Simulated RyR gating data using a published model under identical conditions.
- Analyzed closed time histograms of both experimental and simulated data, with and without filtering.
Main Results:
- At 10 kHz resolution, both experimental and simulated RyR activity showed three exponential closed time components.
- Closed times from simulated data closely matched experimental findings.
- Filtering data to 2 kHz revealed two exponential closed time components, consistent with prior research.
Conclusions:
- High-resolution recordings reveal three closed times in RyR activity, supporting the multi-ion binding hypothesis.
- The study validates a computational model of RyR gating against experimental data.
- Findings reinforce the concept that ryanodine receptors require binding of multiple calcium ions to open.
Abstract:
Measurements of ryanodine receptor (RyR) activity during dynamic changes of calcium concentration have suggested that RyR has at least four calcium binding sites, and that activation transpires as an increase in the activity within the high open probability H-mode. Binding of several Ca2+ ions within the H-mode should manifest itself in the steady-state RyR activity by the presence of multiple closed times. However, previously only two closed times were detected in the H-mode of RyR activity. Here we recorded steady-state activity of single cardiac RyRs with high temporal resolution and compared it to data simulated under the same conditions using our previously published model of RyR gating. At a 10 kHz resolution, the closed time histograms of both experimental and simulated data had three exponential components. The closed times of simulated data were not significantly different from those obtained experimentally. After filtering at 2 kHz, only two exponential closed time components with time constants not significantly different from those previously published could be detected in both experimental and simulated records. The conformity of the steady-state experimental data to the model derived from the dynamic data provides further support for the idea that RyRs need binding of multiple Ca2+ ions to open.
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