title: Developmental changes in calcium/calmodulin-dependent inactivation of calcium currents at the rat calyx of Held.
abstract: 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.
authors.affiliation: Doshisha University, Faculty of Life and Medical Sciences, Kyoto 619-0225, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamashita
authors.forename: Naoto
authors.initials: N
authors.lastname: Saitoh
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000196:embryology* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002147:Calmodulin; D002118:Calcium