%0 Journal Article %1 Klin_1997_674 %A Klingauf, J. %A Neher, E. %D 1997 %J Biophys. J. %K 9017195 Action Animals, Biological, Calcium Calcium, Catecholamines, Cattle, Cell Cells, Channe, Chromaffin Diffusion, Electrophysiology, Exocytosis, Fusion, Gov't, Kinetics, Membrane Membrane, Models, Non-U.S. Potentials, Research Support, ls, %N 2 Pt 1 %P 674--690 %T Modeling buffered Ca$^2+$ diffusion near the membrane: implications for secretion in neuroendocrine cells. %U http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=9017195 %V 72 %X Secretion of catecholamines from neuroendocrine cells is relatively slow and it is likely that redistribution and buffering of Ca$^2+$ 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 Ca$^2+$ 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 (Ca$^2+$i) at a release site peaks at < 10 microM 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 Ca$^2+$ channel pore. Peak Ca$^2+$i and the slow decay were well simulated when release-ready granules were randomly distributed within a regular grid of Ca$^2+$ channels with mean interchannel distances of 300-600 nm. For such large spacings, however, the initial rise in Ca$^2+$i was underestimated, suggesting that a small fraction of the release-ready pool (approximately 10\%) experiences much higher Ca$^2+$i, and thus might be colocalized with Ca$^2+$ 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 Ca$^2+$ not only in triggering, but also in modulating the secretory response: buffers are locally depleted by residual Ca$^2+$ of a preceding stimulus, so that a second pulse leads to a larger peak Ca$^2+$i at the fusion sites.

@article{Klin_1997_674, abstract = {Secretion of catecholamines from neuroendocrine cells is relatively slow and it is likely that redistribution and buffering of {C}a$^{2+}$ 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 {C}a$^{2+}$ 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 ([{C}a$^{2+}$]i) at a release site peaks at < 10 microM 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 {C}a$^{2+}$ channel pore. Peak [{C}a$^{2+}$]i and the slow decay were well simulated when release-ready granules were randomly distributed within a regular grid of {C}a$^{2+}$ channels with mean interchannel distances of 300-600 nm. For such large spacings, however, the initial rise in [{C}a$^{2+}$]i was underestimated, suggesting that a small fraction of the release-ready pool (approximately 10\%) experiences much higher [{C}a$^{2+}$]i, and thus might be colocalized with {C}a$^{2+}$ 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 {C}a$^{2+}$ not only in triggering, but also in modulating the secretory response: buffers are locally depleted by residual {C}a$^{2+}$ of a preceding stimulus, so that a second pulse leads to a larger peak [{C}a$^{2+}$]i at the fusion sites.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Klingauf, J. and Neher, E.}, biburl = {https://www.bibsonomy.org/bibtex/2c169624e001dd76ec0c3d2524ca8d006/hake}, description = {The whole bibliography file I use.}, file = {Klin_1997_674.pdf:Klin_1997_674.pdf:PDF}, interhash = {275594f74e5a5e22d077ed017b961425}, intrahash = {c169624e001dd76ec0c3d2524ca8d006}, journal = {Biophys. J.}, keywords = {9017195 Action Animals, Biological, Calcium Calcium, Catecholamines, Cattle, Cell Cells, Channe, Chromaffin Diffusion, Electrophysiology, Exocytosis, Fusion, Gov't, Kinetics, Membrane Membrane, Models, Non-U.S. Potentials, Research Support, ls,}, month = Feb, number = {2 Pt 1}, pages = {674--690}, pmid = {9017195}, timestamp = {2009-06-03T11:21:18.000+0200}, title = {Modeling buffered {C}a$^{2+}$ diffusion near the membrane: implications for secretion in neuroendocrine cells.}, url = {http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=9017195}, volume = 72, year = 1997 }