Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 344K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ogden, D. Articles by Capiod, T. Search for Related Content PubMed PubMed Citation Articles by Ogden, D. Articles by Capiod, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Social Bookmarking                            What's this?

Article

From the Division of Neurophysiology, National Institute for Medical Research, London NW7 1AA, United Kingdom

The repetitive spiking of free cytosolic [Ca²⁺] ([Ca²⁺]_i) during hormonal activation of hepatocytes depends on the activation and subsequent inactivation of InsP₃-evoked Ca²⁺ release. The kinetics of both processes were studied with flash photolytic release of InsP₃ and time resolved measurements of [Ca²⁺]_i in single cells. InsP₃ evoked Ca²⁺ flux into the cytosol was measured as d[Ca²⁺]_i/dt, and the kinetics of Ca²⁺ release compared between hepatocytes and cerebellar Purkinje neurons. In hepatocytes release occurs at InsP₃ concentrations greater than 0.1–0.2 µM. A comparison with photolytic release of metabolically stable 5-thio-InsP₃ suggests that metabolism of InsP₃ is important in determining the minimal concentration needed to produce Ca²⁺ release. A distinct latency or delay of several hundred milliseconds after release of low InsP₃ concentrations decreased to a minimum of 20–30 ms at high concentrations and is reduced to zero by prior increase of [Ca²⁺]_i, suggesting a cooperative action of Ca²⁺ in InsP₃ receptor activation. InsP₃-evoked flux and peak [Ca²⁺]_i increased with InsP₃ concentration up to 5–10 µM, with large variation from cell to cell at each InsP₃ concentration. The duration of InsP₃-evoked flux, measured as 10–90% risetime, showed a good reciprocal correlation with d[Ca²⁺]_i/dt and much less cell to cell variation than the dependence of flux on InsP₃ concentration, suggesting that the rate of termination of the Ca²⁺ flux depends on the free Ca²⁺ flux itself. Comparing this data between hepatocytes and Purkinje neurons shows a similar reciprocal correlation for both, in hepatocytes in the range of low Ca²⁺ flux, up to 50 µM · s^–1 and in Purkinje neurons at high flux up to 1,400 µM · s^–1. Experiments in which [Ca²⁺]_i was controlled at resting or elevated levels support a mechanism in which InsP₃-evoked Ca²⁺ flux is inhibited by Ca²⁺ inactivation of closed receptor/channels due to Ca²⁺ accumulation local to the release sites. Hepatocytes have a much smaller, more prolonged InsP₃-evoked Ca²⁺ flux than Purkinje neurons. Evidence suggests that these differences in kinetics can be explained by the much lower InsP₃ receptor density in hepatocytes than Purkinje neurons, rather than differences in receptor isoform, and, more generally, that high InsP₃ receptor density promotes fast rising, rapidly inactivating InsP₃-evoked [Ca²⁺]_i transients.

Key Words: liver • Purkinje neurons • calcium • InsP₃ • flash photolysis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. V. Sarkisov, S. E. Gelber, J. W. Walker, and S. S.-H. Wang Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate J. Biol. Chem., August 31, 2007; 282(35): 25517 - 25526. [Abstract] [Full Text] [PDF]

				J. K. Foskett, C. White, K.-H. Cheung, and D.-O. D. Mak Inositol Trisphosphate Receptor Ca2+ Release Channels Physiol Rev, April 1, 2007; 87(2): 593 - 658. [Abstract] [Full Text] [PDF]

				L. Ionescu, K.-H. Cheung, H. Vais, D.-O. D. Mak, C. White, and J. K. Foskett Graded recruitment and inactivation of single InsP3 receptor Ca2+-release channels: implications for quartal Ca2+release J. Physiol., June 15, 2006; 573(3): 645 - 662. [Abstract] [Full Text] [PDF]

				M. Canepari and D. Ogden Kinetic, pharmacological and activity-dependent separation of two Ca2+ signalling pathways mediated by type 1 metabotropic glutamate receptors in rat Purkinje neurones J. Physiol., May 15, 2006; 573(1): 65 - 82. [Abstract] [Full Text] [PDF]

				S. N. Jacob, C.-U. Choe, P. Uhlen, B. DeGray, M. F. Yeckel, and B. E. Ehrlich Signaling Microdomains Regulate Inositol 1,4,5-Trisphosphate-Mediated Intracellular Calcium Transients in Cultured Neurons J. Neurosci., March 16, 2005; 25(11): 2853 - 2864. [Abstract] [Full Text] [PDF]

				M. Canepari, C. Auger, and D. Ogden Ca2+ Ion Permeability and Single-Channel Properties of the Metabotropic Slow EPSC of Rat Purkinje Neurons J. Neurosci., April 7, 2004; 24(14): 3563 - 3573. [Abstract] [Full Text] [PDF]

				F. W. Johenning, M. Zochowski, S. J. Conway, A. B. Holmes, P. Koulen, and B. E. Ehrlich Distinct Intracellular Calcium Transients in Neurites and Somata Integrate Neuronal Signals J. Neurosci., July 1, 2002; 22(13): 5344 - 5353. [Abstract] [Full Text] [PDF]

				J. E. Swatton and C. W. Taylor Fast Biphasic Regulation of Type 3 Inositol Trisphosphate Receptors by Cytosolic Calcium J. Biol. Chem., May 10, 2002; 277(20): 17571 - 17579. [Abstract] [Full Text] [PDF]

				D. R Giovannucci, J. I. E Bruce, S. V Straub, J. Arreola, J. Sneyd, T. J Shuttleworth, and D. I Yule Cytosolic Ca2+ and Ca2+-activated Cl- current dynamics: insights from two functionally distinct mouse exocrine cells J. Physiol., April 15, 2002; 540(2): 469 - 484. [Abstract] [Full Text] [PDF]

				S. Tertyshnikova and A. Fein Dual Regulation of Calcium Mobilization by Inositol 1,4,5-Trisphosphate in a Living Cell J. Gen. Physiol., April 1, 2000; 115(4): 481 - 490. [Abstract] [Full Text] [PDF]

				J F Kidd, K E Fogarty, R A Tuft, and P Thorn The role of Ca2+ feedback in shaping InsP3-evoked Ca2+ signals in mouse pancreatic acinar cells J. Physiol., October 1, 1999; 520(1): 187 - 201. [Abstract] [Full Text] [PDF]

				R. Lux, V. R. N. Munasinghe, F. Castellano, J. W. Lengeler, J. E. T. Corrie, and S. Khan Elucidation of a PTS-Carbohydrate Chemotactic Signal Pathway in Escherichia coli Using a Time-resolved Behavioral Assay Mol. Biol. Cell, April 1, 1999; 10(4): 1133 - 1146. [Abstract] [Full Text]

				T. Capiod ATP-activated cation currents in single guinea-pig hepatocytes J. Physiol., March 15, 1998; 507(3): 795 - 805. [Abstract] [Full Text] [PDF]

				J. Sneyd and J.-F. Dufour A dynamic model of the type-2 inositol trisphosphate receptor PNAS, February 19, 2002; 99(4): 2398 - 2403. [Abstract] [Full Text] [PDF]

				H. Morikawa, F. Imani, K. Khodakhah, and J. T. Williams Inositol 1,4,5-Triphosphate-Evoked Responses in Midbrain Dopamine Neurons J. Neurosci., October 15, 2000; 20(20): RC103 - RC103. [Abstract] [Full Text] [PDF]

				D. R Giovannucci, J. I. E Bruce, S. V Straub, J. Arreola, J. Sneyd, T. J Shuttleworth, and D. I Yule Cytosolic Ca2+ and Ca2+-activated Cl- current dynamics: insights from two functionally distinct mouse exocrine cells J. Physiol., April 15, 2002; 540(2): 469 - 484. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents