Developmental changes in calcium/calmodulin-dependent inactivation of calcium currents at the rat calyx of Held
Developmental changes in calcium/calmodulin-dependent inactivation of calcium currents at the rat calyx of Held
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DOI：
10.1113/jphysiol.2007.142521
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发表时间：
2008-05-01
影响因子：
5.5
通讯作者：
Takahashi, Tomoyuki
中科院分区：
文献类型：
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作者：
Nakamura, Takeshi;Yamashita, Takayuki;Takahashi, Tomoyuki
Ca2+结合钙调素（CaM）引起重组Ca2+通道的促进和/或失活。在大鼠的Held花萼，在听力发作之前，突触前Ca2+电流（I-pCa）在1hz左右的重复激活期间经历Ca2+/ cam依赖性失活，这意味着这可能是短期突触抑制的主要原因。然而，Ca2+/ cam依赖性I-pCa失活是否在更成熟的动物中持续存在仍然是开放的。为了解决这个问题，我们测试了CaM抑制剂在出生后7-9天(P)和出生后13-15天(P)听力发作前对萼中I-pCa活性依赖性调节的影响。我们的研究结果表明，在低频刺激下，cam依赖性的I-pCa失活，以及随后的突触抑制，只发生在听力前期的萼部。然而，CaM在P8和P14萼中的免疫反应性同样强。即使在P13-15时，高频率刺激（200-500 Hz）也可以诱导I-pCa失活，EGTA （10 mM）或CaM抑制剂肽加载到末端会减弱这种失活。此外，在500 Hz刺激下，CaM抑制剂肽减弱了I-pCa失活前的短暂促进作用，而在50-200 Hz刺激下，它对持续的I-pCa促进作用没有影响。这些结果表明，Ca2+/ cam依赖的I-pCa调制需要高的端内Ca2+浓度，这种浓度可以在低频刺激下在未成熟的萼端达到，但只有在萼端后的异常高频刺激下才能达到。
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 (I-pCa) 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 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 mM) 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 Ca2+/CaM-dependent I-pCa 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.