An <i>I</i>_D-like current that is downregulated by Ca<SUP>2+</SUP> modulates information coding at CA3-CA3 synapses in the rat hippocampus

作     者：Saviane, C Mohajerani, MH Cherubini, E 

作者机构：SISSA Sch Adv Int Studies Neurosci Program I-34014 Trieste Italy SISSA Sch Adv Int Studies Ist Nazl Fis Mat Unit I-34014 Trieste Italy 

出 版 物：《JOURNAL OF PHYSIOLOGY-LONDON》 (生理学杂志)

年 卷 期：2003年第552卷第2期

页      面：513-524页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学] 

主　　题：Anterior-Posterior Action Potentials V (voltage) Potassium measurement 动作电位 IDAHO OPERATIONS OFFICE Action Potentials synaptic efficacy Information coding Conductance 

摘      要：Voltage-gated K+ channels localised on presynaptic nerve terminals control information coding by modulating presynaptic firing and synaptic efficacy in target neurones. We found that at CA3-CA3 connections in hippocampal slice cultures, a fast-activating, slowly inactivating K+ conductance similar to the so-called delay current (I-D) is responsible for the delayed appearance of the first spike upon membrane depolarisation, for action potential repolarisation and for modulation of transmitter release. The I-D-like current was downregulated by intracellular Ca2+, as indicated by the increased delay in the appearance of the first action potential following either the block of Ca2+ flux through voltage-dependent Ca2+ channels with Cd2+ or replacement of the bathing solution with one devoid of Ca2+. In both cases, this effect was reversed by blocking this conductance with a low concentration of 4-aminopyridine (4-AP, 10-50 am). Application of 4-AP shortened the delay to the first spike generation, prevented the effect of Cd2+ and increased the spike duration. The earlier appearance of the first action potential was also observed in the presence of dendrotoxin-1 (100 nM). In voltage-clamp experiments larger currents were recorded in the absence of extracellular Ca2+, thus confirming the downregulation of the I-D-like current by Ca2+ due to the positive shift of its inactivation. Spike broadening was associated with an enhancement of synaptic efficacy in target neurones, as assessed by the increase in EPSC amplitude and in the percentage of successes. Moreover, in the presence of 4-AP, EPSCs appeared with a longer latency and were more scattered. This conductance is therefore crucial for setting the timing and strength of synaptic transmission at CA3-CA3 connections. It is conceivable that switching off I-D by increasing intracellular Ca2+ following activity-dependent processes may facilitate network synchronisation and crosstalk between CA3 pyramidal cells, leading to sei