Pflügers Archiv

, Volume 448, Issue 2, pp 161–174 | Cite as

Modeling of stimulation–secretion coupling in a chromaffin cell

  • A. WarashinaEmail author
  • T. Ogura
Cell and Molecular Physiology


We constructed a chromaffin cell model for analysis of stimulation–secretion coupling in computer simulation studies. The model includes mechanisms involved in the excitatory synapse, voltage-dependent Na+, K+ and Ca2+ channels, Ca2+-activated K+ channels (SK type), buffered Ca2+ diffusion, Ca2+ extrusion, fluorescent Ca2+ indicators and Ca2+-triggered exocytosis. Calculations of the modeled mechanisms were carried out using the NEURON simulation environment (Hines and Carnevale, Neural Computation 9:1179–1209, 1997). A set of parameter values was determined so as to fit basic experimental results reported in the literature. The model was also applied to simulate our experimental results obtained from chromaffin cells in the perfused rat adrenal medulla. Observed profiles of Ca2+responses induced by electrically stimulating the splanchnic nerve with various frequencies (1–50 Hz) were adequately simulated with minor readjustments of parameter values for Ca2+influx and extrusion. Secretory responses measured at the same time as the Ca2+responses were also simulated with consideration of a time constant to detect catecholamines in the experiment. Similarly, model simulations reproduced both Ca2+responses and secretory responses evoked by elevations of the extracellular K+ concentration for different periods. The results suggest that the presented model provides a useful tool for analyzing and predicting quantitative relations in various events occurring in stimulation–secretion coupling in chromaffin cells.


Chromaffin cell model  Computer simulation Stimulation–secretion coupling  



This study was supported in part by NIH/NIDCD grants DC 05140 (TO) and P30 DC 04657 (Diego Restrepo of Univ. Colorado Health Sciences Center).


  1. 1.
    Barbara J-G, Takeda K (1996) Quantal release at a neuronal nicotinic synapse from rat adrenal gland. Proc Natl Acad Sci USA 93:9905–9909CrossRefPubMedGoogle Scholar
  2. 2.
    Destexhe A, Contreras D, Sejnowski TJ, Steriade M (1994) A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J Neurophysiol 72:803–818PubMedGoogle Scholar
  3. 3.
    Gandía L, Borges R, Albillos A, García AG (1995) Multiple calcium channel subtypes in isolated rat chromaffin cells. Pflugers Arch 430:55–63PubMedGoogle Scholar
  4. 4.
    Heinemann C, Rüden LV, Chow RH, Neher E (1993) A two-step model of secretion control in neuroendocrine cells. Pflugers Arch 424:105–112PubMedGoogle Scholar
  5. 5.
    Hines ML, Carnevale NT (1997) The NEURON simulation environment. Neural Comput 9:1179–1209PubMedGoogle Scholar
  6. 6.
    Hines ML, Carnevale NT (2000) Expanding NEURON‘s repertoire of mechanisms with NMODL. Neural Comput 12:995–1007CrossRefPubMedGoogle Scholar
  7. 7.
    Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (Lond) 117:500-544Google Scholar
  8. 8.
    Horrigan FT, Bookman RJ (1994) Releasable pools and the kinetics of exocytosis in adrenal chromaffin cells. Neuron 13:1119–1129PubMedGoogle Scholar
  9. 9.
    Kajiwara R, Sand O, Kidokoro Y, Barish ME, Iijima T (1997) Functional organization of chromaffin cells and cholinergic synaptic transmission in rat adrenal medulla. Jpn J Physiol 47:449–464PubMedGoogle Scholar
  10. 10.
    Kidokoro Y, Miyazaki S, Ozawa S (1982) Acetylcholine-induced membrane depolarization and potential fluctuations in the rat adrenal chromaffin cell. J Physiol (Lond) 324:203–220Google Scholar
  11. 11.
    Kitamura N, Ohta T, Ito S, Nakazato Y (1997) Calcium channel subtypes in porcine adrenal chromaffin cells. Pflugers Arch 434:179–187CrossRefPubMedGoogle Scholar
  12. 12.
    Klingauf J, Neher E (1997) Modeling buffered Ca2+diffusion near the membrane: implications for secretion in neuroendocrine cells. Biophys J 72:674–690PubMedGoogle Scholar
  13. 13.
    Kumakura K, Sato A, Suzuki H (1988) Direct recording of the total catecholamine secretion from the adrenal gland in response to splanchnic nerve stimulation in rats. J Neurosci Methods 24:39–43CrossRefPubMedGoogle Scholar
  14. 14.
    McCormick DA, Huguenard JR (1992) A model of the electrophysiological properties of thalamocortical relay neurons. J Neurophysiol 68:1384–1400PubMedGoogle Scholar
  15. 15.
    Moser T, Neher E (1997) Rapid exocytosis in single chromaffin cells recorded from mouse adrenal slices. J Neurosci 17:2314–2323PubMedGoogle Scholar
  16. 16.
    Neely A, Lingle CJ (1992) Two components of calcium-activated potassium current in rat adrenal chromaffin cells. J Physiol (Lond) 453:97–131Google Scholar
  17. 17.
    Park YB (1994) Ion selectivity and gating of small conductance Ca2+-activated K+ channels in cultured rat adrenal chromaffin cells. J Physiol (Lond) 481:555–570Google Scholar
  18. 18.
    Prakriya M, Solaro CR, Lingle CJ (1996) [Ca2+]i elevations detected by BK channels during Ca2+influx and muscarine-mediated release of Ca2+from intracellular stores in rat chromaffin cells. J Neurosci 16:4344–4359PubMedGoogle Scholar
  19. 19.
    Sala F, Hernández-Cruz A (1990) Calcium diffusion modeling in a spherical neuron: relevance of buffering properties. Biophys J 57:313–324Google Scholar
  20. 20.
    Smith C, Moser T, Xu T, Neher E (1998) Cytosolic Ca2+ acts by two separate pathways to modulate the supply of release-competent vesicles in chromaffin cells. Neuron 20:1243–1253PubMedGoogle Scholar
  21. 21.
    Solaro CR, Prakriya M, Ding JP, Lingle CJ (1995) Inactivating and Noninactivating Ca2+and voltage-dependent K+ current in rat adrenal chromaffin cells. J Neurosci 15:6110–6123PubMedGoogle Scholar
  22. 22.
    Tomlinson A, Durbin J, Coupland RE (1987) A quantitative analysis of rat adrenal chromaffin tissue: morphometric analysis at tissue and cellular level correlated with catecholamine content. Neuroscience 20:895–904CrossRefPubMedGoogle Scholar
  23. 23.
    Voets T (2000) Dissection of three Ca2+-dependent steps leading to secretion in chromaffin cells from mouse adrenal slices. Nueron 28:537–545Google Scholar
  24. 24.
    Wakade AR (1981) Studies on secretion of catecholamines evoked by acetylcholine or transmural stimulation of the rat adrenal gland. J Physiol (Lond) 313:463–480Google Scholar
  25. 25.
    Warashina A (1999) Light-evoked recovery from wortmannin-induced inhibition of catecholamine secretion and synaptic transmission. Arch Biochem Biophys 367:330–310CrossRefGoogle Scholar
  26. 26.
    Warashina A (2001) Mechanism by which wortmannin and LY294002 inhibit catecholamine secretion in the rat adrenal medullary cells. Cell Calcium 29:239–247CrossRefPubMedGoogle Scholar
  27. 27.
    Warashina A, Satoh Y (2001) Modes of secretagogue-induced [Ca2+]i responses in individual chromaffin cells of the perfused rat adrenal medulla. Cell Calcium 30:395–401CrossRefPubMedGoogle Scholar
  28. 28.
    Xu T, Naraghi M, Kang H, Neher E (1997) Kinetic studies of Ca2+binding and Ca2+clearance in the cytosol of adrenal chromaffin cells. Biophys J 73:532–545PubMedGoogle Scholar
  29. 29.
    Yamada WM, Koch C, Adams PR (1989) Multiple channels and calcium dynamics. In: Koch C, Segev I (eds) Method in neuronal modeling. MIT Press, pp 137-170Google Scholar
  30. 30.
    Zhou Z, Neher E (1993) Mobile and immobile calcium buffers in bovine adrenal chromaffin cells. J Physiol (Lond) 469:245–273Google Scholar

Copyright information

© Springer-Verlag  2004

Authors and Affiliations

  1. 1.Division of Cell PhysiologyNiigata University Graduate School of Medical and Dental SciencesNiigata Japan
  2. 2.Department of Biomedical SciencesColorado State UniversityFort CollinsUSA
  3. 3.Department of Cellular and Structural BiologyUniversity of Colorado Health Sciences CenterDenverUSA

Personalised recommendations