Biophysical Journal 72: 674-690 (1997)
© 1997 the Biophysical Society

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Modeling Buffered Ca²⁺ Diffusion Near the Membrane

Implications for Secretion in Neuroendocrine Cells

Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, D-37077 Göttingen, Germany

ABSTRACT

Secretion of catecholamines from neuroendocrine cells is relatively slow and it is likely that redistribution and buffering of Ca²⁺ is a major factor for delaying the response after a stimulus. In fact, in a recent study (Chow, R. H., J. Klingauf, and E. Neher. 1994. Time course of Ca²⁺ concentration triggering exocytosis in neuroendocrine cells. Proc. Natl. Acad. Sci. U.S.A. 91:12765-12769) Chow et al. concluded that the concentration of free calcium ([Ca²⁺]_i) at a release site peaks at <10 µM during short-step depolarizations, and then decays to baseline over tens of milliseconds. To check whether such a time course is consistent with diffusion theory, we modeled buffered diffusion in the vicinity of a Ca²⁺ channel pore. Peak [Ca²⁺]_i and the slow decay were well simulated when release-ready granules were randomly distributed within a regular grid of Ca²⁺ channels with mean interchannel distances of 300-600 nm. For such large spacings, however, the initial rise in [Ca²⁺]_i was underestimated, suggesting that a small fraction of the release-ready pool (10%) experiences much higher [Ca²⁺]_i, and thus might be collocalized with Ca²⁺ channels. A model that accommodates these findings then correctly predicts many recent observations, including the result that single action potentials evoke near-synchronous transmitter release with low quantal yield, whereas trains of action potentials lead to desynchronized release, but with severalfold increased quantal yield. The simulations emphasize the role of Ca²⁺ not only in triggering, but also in modulating the secretory response: buffers are locally depleted by residual Ca²⁺ of a preceding stimulus, so that a second pulse leads to a larger peak [Ca²⁺]_i at the fusion sites.

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