Key result
Langevin Ca2+ channel models approximate Markov chains and show intermediate inactivation causes negatively correlated puffs.
Why the study?
A Langevin description of stochastic Ca2+ release may approximate Markov chain models for physiological numbers of Ca2+ channels per release unit, but the impact on puff/spark statistics and correlations is unclear.
This computational study demonstrates that a Langevin model effectively approximates Markov chain models for Ca2+ release and reveals how inactivation kinetics govern the correlations between successive Ca2+ sparks.
Facilitates scalable Ca2+ puff modeling; leaves open validation of inactivation-rate effects in cells.
Through theoretical analysis of the statistics of stochastic calcium (Ca 2+ ) release (i.e., the amplitude, duration and inter-event interval of simulated Ca 2+ puffs and sparks), we show that a Langevin description of the collective gating of Ca 2+ channels may be a good approximation to the corresponding Markov chain model when the number of Ca 2+ channels per Ca 2+ release unit (CaRU) is in the physiological range. The Langevin description of stochastic Ca 2+ release facilitates our investigation of correlations between successive puff/spark amplitudes, durations and inter-spark intervals, and how such puff/spark statistics depend on the number of channels per release site and the kinetics of Ca 2+ -mediated inactivation of open channels. When Ca 2+ inactivation/de-inactivation rates are intermediate—i.e., the termination of Ca 2+ puff/sparks is caused by the recruitment of inactivated channels—the correlation between successive puff/spark amplitudes is negative, while the correlations between puff/spark amplitudes and the duration of the preceding or subsequent inter-spark interval are positive. These correlations are significantly reduced when inactivation/deinactivation rates are extreme (slow or fast) and puff/sparks terminate via stochastic attrition.
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Wang et al. (2015) studied Stochastic calcium release. Langevin description of collective gating of Ca2+ channels vs. Markov chain model was evaluated on Statistics of stochastic calcium release (amplitude, duration, and inter-event interval). A Langevin description of collective Ca2+ channel gating approximates Markov chain models well and shows that intermediate Ca2+ inactivation rates cause negative correlations between successive puff amplitudes.
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