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Competitive Calcium Binding: Implications for Dendritic Calcium Signaling

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Abstract

Action potentials evoke calcium transients in dendrites of neocortical pyramidal neurons with time constants of <100 ms at physiological temperature. This time period may not be sufficient for inflowing calcium ions to equilibrate with all present Ca2+-binding molecules. We therefore explored nonequilibrium dynamics of Ca2+ binding to numerous Ca2+ reaction partners within a dendritelike compartment using numerical simulations. After a brief Ca2+ influx, the reaction partner with the fastest Ca2+ binding kinetics initially binds more Ca2+ than predicted from chemical equilibrium, while companion reaction partners bind less. This difference is consolidated and may result in bypassing of slow reaction partners if a Ca2+ clearance mechanism is active. On the other hand, slower reaction partners effectively bind Ca2+ during repetitive calcium current pulses or during slower Ca2+ influx. Nonequilibrium Ca2+ distribution can further be enhanced through strategic placement of the reaction partners within the compartment. Using the Ca2+ buffer EGTA as a competitor of fluo-3, we demonstrate competitive Ca2+ binding within dendrites experimentally. Nonequilibrium calcium dynamics is proposed as a potential mechanism for differential and conditional activation of intradendritic targets.

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Authors and Affiliations

  1. Department of Neurobiology, Weizmann Institute, Rehovot, 76100, Israel

    Henry Markram

  2. Department of Cell Physiology, Max Planck Institute for Medical Research, Jahnstr. 29, D-69120, Heidelberg, Germany

    Arnd Roth & Fritjof Helmchen

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  1. Henry Markram
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  2. Arnd Roth
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  3. Fritjof Helmchen
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Markram, H., Roth, A. & Helmchen, F. Competitive Calcium Binding: Implications for Dendritic Calcium Signaling. J Comput Neurosci 5, 331–348 (1998). https://doi.org/10.1023/A:1008891229546

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