Figure 4.

Activity-dependent VGCC facilitation. A, Repetitive activation of presynaptic Ca²⁺ currents causes transient facilitation followed by sustained inactivation of VGCCs at the calyx of Held.⁵¹⁾ B, Paired-pulse presynaptic stimulation using AP-waveform command pulses (top trace) induces facilitation of VGCCs (second traces) and ensuing EPSC facilitation (bottom trace) at the calyx of Held (left panel). Manual attenuation of the AP-waveform command pulse amplitude to cancel VGCC facilitation reduces EPSC facilitation (right panel). The percentage contribution of VGCC facilitation to EPSC facilitation is about 50%, irrespective of the intracellular Ca²⁺ buffer strength (lower bar graphs).⁵⁸⁾ In these experiments, p is lowered with botulinum toxin E included in presynaptic pipettes to minimize synaptic depression. C, VGCC facilitation during repetitive stimulation at the calyx of Held in wild type mice (WT, upper panel, with sample records in inset) and VGCC inactivation in P/Q-type VGCC knockout mice, where N-type VGCCs take over the P/Q-type VGCC current (lower panel).⁶⁰⁾