Kinetics of Cardiac RyR
Channel Gating Studied at High Temporal Resolution
M. DURA, I. ZAHRADNÍK, A. ZAHRADNÍKOVÁ
Institute of Molecular Physiology and Genetics, Slovak Academy
of Sciences, Bratislava, Slovak Republic
Received August 30, 2002
Accepted November 1, 2002
Summary
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.
Key words
Ryanodine receptor • Gating • Kinetics • Calcium release •
Cardiac muscle
Reprint requests
Alexandra Zahradníková, Institute of Molecular Physiology and
Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34
Bratislava, Slovak Republic. Fax: +421 2 5477 3666, e-mail:
umfgzahr@kramare.savba.sk
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