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

Takeshi Nakamura, Takayuki Yamashita, Naoto Saitoh, Tomoyuki Takahashi

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26 Citations (Scopus)


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 I pCa 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 I pCa 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.

Original languageEnglish
Pages (from-to)2253-2261
Number of pages9
JournalJournal of Physiology
Issue number9
Publication statusPublished - 01-05-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology


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