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 te mperature. This time period may not be sufficient for inflowing calciu m ions to equilibrate with all present Ca2+-binding molecules. We ther efore 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 les s. This difference is consolidated and may result in bypassing of slow reaction partners if a Ca2+ clearance mechanism is active. On the oth er hand, slower reaction partners effectively bind Ca2+ during repetit ive calcium current pulses or during slower Ca2+ influx. Nonequilibriu m Ca2+ distribution can further be enhanced through strategic placemen t of the reaction partners within the compartment. Using the Ca2+ buff er EGTA as a competitor of fluo-3, we demonstrate competitive Ca2+ bin ding within dendrites experimentally. Nonequilibrium calcium dynamics is proposed as a potential mechanism for differential and conditional activation of intradendritic targets.