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Developmental changes in calcium/calmodulin‐dependent inactivation of calcium currents at the rat calyx of Held

Ca2+‐binding to calmodulin (CaM) causes facilitation and/or inactivation of recombinant Ca2+ channels. At the rat calyx of Held, before hearing onset, presynaptic Ca2+ currents (IpCa) undergo Ca2+/CaM‐dependent inactivation during repetitive activation at around 1 Hz, implying that this may be a major cause of short‐term synaptic depression. However, it remains open whether the Ca2+/CaM‐dependent inactivation of IpCa persists in more mature animals. To address this question, we tested the effect of CaM inhibitors on the activity‐dependent modulation of IpCa in calyces, before (postnatal day (P) 7–9) and after (P13–15) hearing onset. Our results indicate that the CaM‐dependent IpCa inactivation during low‐frequency stimulation, and the ensuing synaptic depression, occur only at calyces in the prehearing period. However, CaM immunoreactivity in P8 and P14 calyces was equally strong. Even at P13–15, high frequency stimulation (200–500 Hz) could induce IpCa inactivation, which was attenuated by EGTA (10 mm) or a CaM inhibitor peptide loaded into the terminal. Furthermore, the CaM inhibitor peptide attenuated a transient facilitation of IpCa preceding inactivation observed at 500 Hz stimulation, whereas it had no effect on sustained IpCa facilitations during trains of 50–200 Hz stimulation. These results suggest that the Ca2+/CaM‐dependent IpCa modulation requires a high intraterminal Ca2+ concentration, which can be attained at immature calyces during low frequency stimulation, but only during unusually high frequency stimulation at calyceal terminals in the posthearing period.