Timing and Efficacy of Ca super(2+) Channel Activation in Hippocampal Mossy Fiber Boutons

The presynaptic Ca super(2+) signal is a key determinant of transmitter release at chemical synapses. In cortical synaptic terminals, however, little is known about the kinetic properties of the presynaptic Ca super(2+) channels. To investigate the timing and magnitude of the presynaptic Ca super(2+) inflow, we performed whole-cell patch-clamp recordings from mossy fiber boutons (MFBs) in rat hippocampus. MFBs showed large high-voltage-activated Ca super(2+) currents, with a maximal amplitude of similar to 100 pA at a membrane potential of 0 mV. Both activation and deactivation were fast, with time constants in the submillisecond range at a temperature of similar to 23 degree C. An MFB action potential (AP) applied as a voltage-clamp command evoked a transient Ca super(2+) current with an average amplitude of similar to 170 pA and a half-duration of 580 mu sec. A prepulse to +40 mV had only minimal effects on the AP-evoked Ca super(2+) current, indicating that presynaptic APs open the voltage-gated Ca super(2+) channels very effectively. On the basis of the experimental data, we developed a kinetic model with four closed states and one open state, linked by voltage-dependent rate constants. Simulations of the Ca super(2+) current could reproduce the experimental data, including the large amplitude and rapid time course of the current evoked by MFB APs. Furthermore, the simulations indicate that the shape of the presynaptic AP and the gating kinetics of the Ca super(2+) channels are tuned to produce a maximal Ca super(2+) influx during a minimal period of time. The precise timing and high efficacy of Ca super(2+) channel activation at this cortical glutamatergic synapse may be important for synchronous transmitter release and temporal information processing.