Abstract
Buffered Ca(2+) diffusion in the cytosol of neuroendocrine cells is a plausible explanation for the slowness and latency in the secretion of hormones. We have developed a Monte Carlo simulation to treat the problem of 3-D diffusion and kinetic reactions of ions and buffers. The 3-D diffusion is modeled as a random walk process that follows the path of each ion and buffer molecule, combined locally with a stochastic treatment of the first-order kinetic reactions involved. Such modeling is able to predict [Ca(2+)] and buffer concentration time courses regardless of how low the calcium influx is, and it is therefore a convenient method for dealing with physiological calcium currents and concentrations. We study the effects of the diffusional and kinetic parameters of the model on the concentration time courses as well as on the local equilibrium of buffers with calcium. An in-mobile and fast endogenous buffer as described by, Biophys. J. 72:674-690) was able to reach local equilibrium with calcium; however, the exogenous buffers considered are displaced drastically from equilibrium at the start of the calcium pulse, particularly below the pores. The versatility of the method also allows the effect of different arrangements of calcium channels on submembrane gradients to be studied, including random distribution of calcium channels and channel clusters. The simulation shows how the particular distribution of channels or clusters can be of relevance for secretion in the case where the distribution of release granules is correlated with the channels or clusters.
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- Allbritton N. L., Meyer T., Stryer L. Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate. Science. 1992 Dec 11;258(5089):1812–1815. doi: 10.1126/science.1465619. [DOI] [PubMed] [Google Scholar]
- Augustine G. J., Charlton M. P., Smith S. J. Calcium entry and transmitter release at voltage-clamped nerve terminals of squid. J Physiol. 1985 Oct;367:163–181. doi: 10.1113/jphysiol.1985.sp015819. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bokvist K., Eliasson L., Ammälä C., Renström E., Rorsman P. Co-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells. EMBO J. 1995 Jan 3;14(1):50–57. doi: 10.1002/j.1460-2075.1995.tb06974.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chow R. H., Klingauf J., Heinemann C., Zucker R. S., Neher E. Mechanisms determining the time course of secretion in neuroendocrine cells. Neuron. 1996 Feb;16(2):369–376. doi: 10.1016/s0896-6273(00)80054-9. [DOI] [PubMed] [Google Scholar]
- Chow R. H., von Rüden L., Neher E. Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells. Nature. 1992 Mar 5;356(6364):60–63. doi: 10.1038/356060a0. [DOI] [PubMed] [Google Scholar]
- Clapham D. E. Calcium signaling. Cell. 1995 Jan 27;80(2):259–268. doi: 10.1016/0092-8674(95)90408-5. [DOI] [PubMed] [Google Scholar]
- Eliasson L., Renström E., Ding W. G., Proks P., Rorsman P. Rapid ATP-dependent priming of secretory granules precedes Ca(2+)-induced exocytosis in mouse pancreatic B-cells. J Physiol. 1997 Sep 1;503(Pt 2):399–412. doi: 10.1111/j.1469-7793.1997.399bh.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klingauf J., Neher E. Modeling buffered Ca2+ diffusion near the membrane: implications for secretion in neuroendocrine cells. Biophys J. 1997 Feb;72(2 Pt 1):674–690. doi: 10.1016/s0006-3495(97)78704-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kruk P. J., Korn H., Faber D. S. The effects of geometrical parameters on synaptic transmission: a Monte Carlo simulation study. Biophys J. 1997 Dec;73(6):2874–2890. doi: 10.1016/S0006-3495(97)78316-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Llinás R., Steinberg I. Z., Walton K. Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse. Biophys J. 1981 Mar;33(3):323–351. doi: 10.1016/S0006-3495(81)84899-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Naraghi M., Müller T. H., Neher E. Two-dimensional determination of the cellular Ca2+ binding in bovine chromaffin cells. Biophys J. 1998 Oct;75(4):1635–1647. doi: 10.1016/S0006-3495(98)77606-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Naraghi M., Neher E. Linearized buffered Ca2+ diffusion in microdomains and its implications for calculation of [Ca2+] at the mouth of a calcium channel. J Neurosci. 1997 Sep 15;17(18):6961–6973. doi: 10.1523/JNEUROSCI.17-18-06961.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neher E. Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron. 1998 Mar;20(3):389–399. doi: 10.1016/s0896-6273(00)80983-6. [DOI] [PubMed] [Google Scholar]
- Nowycky M. C., Pinter M. J. Time courses of calcium and calcium-bound buffers following calcium influx in a model cell. Biophys J. 1993 Jan;64(1):77–91. doi: 10.1016/S0006-3495(93)81342-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olveczky B. P., Verkman A. S. Monte Carlo analysis of obstructed diffusion in three dimensions: application to molecular diffusion in organelles. Biophys J. 1998 May;74(5):2722–2730. doi: 10.1016/S0006-3495(98)77978-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riley M. R., Buettner H. M., Muzzio F. J., Reyes S. C. Monte Carlo simulation of diffusion and reaction in two-dimensional cell structures. Biophys J. 1995 May;68(5):1716–1726. doi: 10.1016/S0006-3495(95)80349-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sala F., Hernández-Cruz A. Calcium diffusion modeling in a spherical neuron. Relevance of buffering properties. Biophys J. 1990 Feb;57(2):313–324. doi: 10.1016/S0006-3495(90)82533-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saxton M. J. Anomalous diffusion due to binding: a Monte Carlo study. Biophys J. 1996 Mar;70(3):1250–1262. doi: 10.1016/S0006-3495(96)79682-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saxton M. J. Anomalous diffusion due to obstacles: a Monte Carlo study. Biophys J. 1994 Feb;66(2 Pt 1):394–401. doi: 10.1016/s0006-3495(94)80789-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. D., Wagner J., Keizer J. Validity of the rapid buffering approximation near a point source of calcium ions. Biophys J. 1996 Jun;70(6):2527–2539. doi: 10.1016/S0006-3495(96)79824-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith P. A., Rorsman P., Ashcroft F. M. Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic beta-cells. Nature. 1989 Nov 30;342(6249):550–553. doi: 10.1038/342550a0. [DOI] [PubMed] [Google Scholar]
- Wagner J., Keizer J. Effects of rapid buffers on Ca2+ diffusion and Ca2+ oscillations. Biophys J. 1994 Jul;67(1):447–456. doi: 10.1016/S0006-3495(94)80500-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Xu T., Naraghi M., Kang H., Neher E. Kinetic studies of Ca2+ binding and Ca2+ clearance in the cytosol of adrenal chromaffin cells. Biophys J. 1997 Jul;73(1):532–545. doi: 10.1016/S0006-3495(97)78091-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamada W. M., Zucker R. S. Time course of transmitter release calculated from simulations of a calcium diffusion model. Biophys J. 1992 Mar;61(3):671–682. doi: 10.1016/S0006-3495(92)81872-6. [DOI] [PMC free article] [PubMed] [Google Scholar]