Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics
Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics
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DOI：
10.1111/j.1469-7793.2001.0807h.x
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发表时间：
2001-03-15
影响因子：
5.5
通讯作者：
Neher, E
中科院分区：
文献类型：
--
作者：
Rozov, A;Burnashev, N;Neher, E
1.在幼年大鼠（出生后14-15天（P））躯体感觉皮层第2/3层锥体细胞的神经末梢与双簇状中间神经元之间的连接中，突触传递的有效性和可靠性较低。在这些连接处，通过成对脉冲刺激（10 Hz）促进释放。在连接形成的第2/3层金字塔的终端与多极神经元的疗效和可靠性高，并通过双脉冲刺激抑制释放。在两种终末中，控制递质释放的电压依赖性钙通道均以P/Q-和N-亚型为主。易化终末的单位EPSP振幅与细胞外钙离子浓度（[Ca 2 +]（o））的关系比抑制终末的更陡。拟合Hill方程（n（H）= 4）表明，抑制性终末的Ca 2+感受器释放囊泡的表观K-nu比促进性终末低2 - 3倍.细胞内负荷的锥体神经元与快速和缓慢作用（钙缓冲剂BAPTA和EGTA差异减少递质释放在这两种类型的终端。突触前BAPTA和EGTA的半数有效浓度分别为0.1和1 mM，可降低刺激双簇细胞锥体细胞诱发的单一EPSP。在较高浓度的突触前BAPTA和EGTA（分别类似于0.5和类似于7 mM）下，多极细胞中诱发的单一EPSP减少到对照的一半.频率依赖性促进的EPSPs在bitufted细胞被废除EGTA在浓度大于或等于0.2 mM，这表明游离Ca 2+的积累是必不可少的促进终端接触bitufted细胞。与此相反，促进不受影响，甚至略有增加，在终端加载BAPTA的浓度范围为0.02-0.5 mM。这是由于部分饱和的外源性添加BAPTA。然而，浓度大于或等于1 mM的BAPTA也消除了促进作用。EGTA对多极细胞EPSPs的频率依赖性抑制作用没有显著降低。使用BAPTA，在浓度> 0.5 mM时，抑郁降低，伴随着训练中第一个EPSP振幅的降低。提出了一种分析，解释了EGTA和BAPTA对突触功效的影响及其在成对脉冲刺激期间在释放位点[Ca 2 +]（[Ca 2 +]（RS））的变化方面的短期修改，并从单一EPSP对[Ca 2 +]（o）的依赖性推断出Ca 2+传感器的亲和力。结果表明，靶细胞特异性的差异，从双簇或多极细胞的终端释放可以解释由一个较长的扩散距离之间的Ca 2+通道和释放网站和/或较低的Ca 2+通道密度在终端接触双簇细胞。这将导致较低的[Ca 2 +]在释放网站，也将解释较高的表观K-上升的Ca 2+传感器在促进终端。
1. In connections formed by nerve terminals of layer 2/3 pyramidal cells onto bitufted interneurones in young (postnatal day (P)14-15) rat somatosensory cortex, the efficacy and reliability of synaptic transmission were low. At these connections release was facilitated by paired-pulse stimulation (at 10 Hz). In connections formed by terminals of layer 2/3 pyramids with multipolar interneurones efficacy and reliability were high and release was depressed by paired-pulse stimulation. In both types of terminal, however, the voltage-dependent Ca2+ channels that controlled transmitter release were predominantly of the P/Q- and N-subtypes.2. The relationship between unitary EPSP amplitude and extracellular calcium concentration ([Ca2+](o)) was steeper for facilitating than for depressing terminals. Fits to a Hill equation with n(H) = 4 indicated that the apparent K-nu of the Ca2+ sensor for vesicle release was two- to threefold lower in depressing terminals than in facilitating ones.3. Intracellular loading of pyramidal neurones with the fast and slowly acting (Ca2+ buffers BAPTA and EGTA differentially reduced transmitter release in these two types of terminal. Unitary EPSPs evoked by pyramidal cell stimulation in bitufted cells were reduced by presynaptic BAPTA and EGTA with half-effective concentrations of similar to0.1 and similar to1 mM, respectively. Unitary EPSPs evoked in multipolar cells were reduced to one-half of control at higher concentrations of presynaptic BAPTA and EGTA (similar to0.5 and similar to7 mM, respectively).4. Frequency-dependent facilitation of EPSPs in bitufted cells was abolished by EGTA at concentrations of greater than or equal to 0.2 mM, suggesting that accumulation of free Ca2+ is essential for facilitation in the terminals contacting bitufted cells. In contrast, facilitation was unaffected or even slightly increased in the terminals loaded with BAPTA in the concentration range 0.02-0.5 mM. This is attributed to partial saturation of exogenously added BAPTA. However, BAPTA at concentrations greater than or equal to 1 mM also abolished facilitation.5. Frequency-dependent depression of EPSPs in multipolar cells was not significantly reduced by EGTA. With BAPTA, the depression decreased at concentrations > 0.5 mM, concomitant with a reduction in amplitude of the first EPSP in a train.6. An analysis is presented that interprets the effects of EGTA and BAPTA on synaptic efficacy and its short-term modification during paired-pulse stimulation in terms of changes in [Ca2+] at the release site ([Ca2+](RS)) and that infers the affinity of the Ca2+ sensor from the dependence of unitary EPSPs on [Ca2+](o).7. The results suggest that the target cell-specific difference in release from the terminals on bitufted or multipolar cells can be explained by a longer diffusional distance between Ca2+ channels and release sites and/or lower Ca2+ channels density in the terminals that contact bitufted cells. This would lead to a lower [Ca2+] at release sites and would also explain the higher apparent K-upsilon of the Ca2+ sensor in facilitating terminals.