Exocytotic dynamics in human chromaffin cells: experiments and modeling

摘要

Chromaffin cells have been widely used to study neurosecretion since they exhibit similar calcium dependence of several exocytotic steps as synaptic terminals do, but having the enormous advantage of being neither as small or fast as neurons, nor as slow as endocrine cells. In the present study, secretion associated to experimental measurements of the exocytotic dynamics in human chromaffin cells of the adrenal gland was simulated by using a model that combines stochastic and deterministic approaches for short and longer depolarizing pulses, respectively. Experimental data were recorded from human chromaffin cells, obtained from healthy organ donors, using the perforated patch configuration of the patch-clamp technique. We have found that in human chromaffin cells, secretion would be mainly managed by small pools of non-equally fusion competent vesicles, slowly refilled over time. Fast secretion evoked by brief pulses can be predicted only when 75% of one of these pools (the "ready re-leasable pool" of vesicles, abbreviated as RRP) are co-localized to Ca~(2+) channels, indicating an immediately releasable pool in the range reported for isolated cells of bovine and rat (Alvarez and Marengo, J Neurochem 116:155-163,2011). The need for spatial correlation and close proximity of vesicles to Ca~(2+) channels suggests that in human chromaffin cells there is a tight control of those releasable vesicles available for fast secretion.