Ca-activation kinetics modulate successive puff/spark amplitude, duration and inter-event-interval correlations in a Langevin model of stochastic Ca release

Through theoretical analysis of the statistics of stochastic calcium (Ca) release (i.e., the amplitude, duration and inter-event interval of simulated Ca puffs and sparks), we show that a Langevin description of the collective gating of Ca channels may be a good approximation to the corresponding Markov chain model when the number of Ca channels per Ca release unit (CaRU) is in the physiological range. The Langevin description of stochastic Ca 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-mediated inactivation of open channels. When Ca inactivation/de-inactivation rates are intermediate—i.e., the termination of Ca 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/de1 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/014431 doi: bioRxiv preprint first posted online Jan. 27, 2015;