Author: Juris Galvanovskis, Oxford University.
Names and affiliation of other authors:
Bo Soderberg, Lund University, Sweden;
Patrik Rorsman, Oxford University, England;
Jovita Karanauskaite, Oxford University, England.
Oral or poster: Poster
The fusion of secretory vesicles and granules with the cell membrane prior to the release of their content into the extra-cellular space requires a transient increase of free Ca2+ concentration in the vicinity of the fusion site. Usually there is a short temporal delay in the onset of the actual fusion of membranes in reference to the risen free Ca2+ levels. This delay is described as a latency time of the Ca2+ sensing system of the secreting machinery and has been observed in several cell types including pancreatic β-cells. The presence of a delay time of a finite length inherent to the secretory machinery of the cell affects in an essential way the probability for a certain granule to fuse with the cell membrane. We have investigated here, theoretically and by numerical simulations, the extent of this influence and its dependence on the parameters of Ca2+ channels, channel clustering, the Ca2+ sensing system, and the length of depolarizing pulses. We used a linear probabilistic model for a random opening and closing of channels that yields an explicit expression for the Laplace transforms of the waiting time distributions for an event that at least one channel is open during the latency time. This allows one to calculate the probability that a vesicle will fuse with the cell membrane during the action potential.