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Developmental changes in calcium/calmodulin‐dependent inactivation of calcium currents at the rat calyx of Held
Author(s) -
Nakamura Takeshi,
Yamashita Takayuki,
Saitoh Naoto,
Takahashi Tomoyuki
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.142521
Subject(s) - stimulation , calmodulin , calcium , calyx , egta , parvalbumin , chemistry , biology , biophysics , microbiology and biotechnology , neuroscience , endocrinology , medicine , anatomy
Ca 2+ ‐binding to calmodulin (CaM) causes facilitation and/or inactivation of recombinant Ca 2+ channels. At the rat calyx of Held, before hearing onset, presynaptic Ca 2+ currents ( I pCa ) undergo Ca 2+ /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 Ca 2+ /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 I pCa in calyces, before (postnatal day (P) 7–9) and after (P13–15) hearing onset. Our results indicate that the CaM‐dependent I pCa 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 I pCa inactivation, which was attenuated by EGTA (10 m m ) or a CaM inhibitor peptide loaded into the terminal. Furthermore, the CaM inhibitor peptide attenuated a transient facilitation of I pCa 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 Ca 2+ /CaM‐dependent I pCa modulation requires a high intraterminal Ca 2+ 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.