Monte Carlo simulation of release of vesicular content in neuroendocrine cells.

The release of transmitter from the vesicle, its diffusion through the fusion pore, and the cleft and its interaction with the carbon electrode were simulated using the Monte Carlo method. According to the simulation the transmitter release is largely determined by geometric factors--the ratio of the fusion pore cross-sectional and vesicular areas, if the diffusion constant is as in the aqueous solution--but the speed of transmitter dissociation from the gel matrix plays an important role during the rise phase of release. Transmitter is not depleted near the entrance to the fusion pore and there is no cleft-to-vesicle feedback, but the depletion becomes evident if the diffusion constant is reduced, especially if the pore is wide. In general, the time course of amperometric currents closely resembles the time course of the simulated transmitter concentration in the cleft and the time course of release. Surprisingly, even a tenfold change of the electrode efficiency has only a marginal effect on the amplitude or the time course of amperometric currents. Greater electrode efficiency however lowers the cleft concentration, but only if the cleft is narrow. As the cleft widens the current amplitudes diminish and rise times lengthen, but the decay times are less affected. Moreover, the amplitude dependence of the rise and decay times becomes steeper as the cleft widens and/or as the release kinetics slows. Finally, lower diffusion constant of transmitter in the narrow cleft does not further prolong the amperometric currents, whose slow time course reflects slow release kinetics.