Competitive calcium binding: Implications for dendritic calcium signaling

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.