Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons
Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons
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DOI：
10.1152/jn.1999.82.4.1895
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发表时间：
1999-10-01
影响因子：
2.5
通讯作者：
Carruth, M
中科院分区：
文献类型：
--
作者：
Magee, JC;Carruth, M
用全细胞膜片钳技术记录成年大鼠海马脑片CAI锥体神经元的索马体和树突，研究树突电压门控离子通道在动作电位爆发产生中的作用。在控制条件下，体细胞电流注射诱发与后超极化（AHP）相关的单个动作电位。4-氨基吡啶（4-AP）的远端顶端树突分支的局部应用后，相同的电流注射导致产生后去极化（ADP）和多个动作电位。将4-AP局部应用于索马/近端树突后，未观察到这种爆发放电。树突状4-AP的应用程序允许大幅度的Na+依赖性动作电位，这是在持续时间延长，反向传播到远端顶端树突。近端4-AP应用未观察到动作电位反向传播的变化。非特异性二价钙通道阻断剂NiCl和CdCl均可抑制ADP和动作电位爆发。Ca 2+通道阻断也降低了树突状细胞动作电位时程，但对峰电位幅度无显著影响。低浓度的TTX（10-50 nM）也降低了CAI神经元在破坏模式下放电的能力。这种效应被认为是抑制反向传播的树突状细胞动作电位的结果，可以克服通过协调注射的瞬态，大幅度去极化电流到树突。树突状电流注射能够恢复：即使在高浓度的TTX（300-500 μ M）的存在下，突发放电模式（表示为一个大的ADP）。这些数据表明树突Na+通道在爆发中的作用是允许体细胞/轴突动作电位反向传播到树突中，然后在树突中激活树突Ca 2+通道。尽管大多数Ca 2+通道亚型在爆发产生中似乎是重要的，但通过NiCl（75 μ M）阻断T-和R-型Ca 2+通道比L-通道（10 μ M尼莫地平）或N-、P/Q-型（1 μ M ω-芋螺毒素MVIIC）Ca 2+通道阻断在更大程度上抑制动作电位爆发。这表明，镍敏感的电压门控钙通道在动作电位爆发的产生中具有最重要的作用。总之，这些数据表明，树突状电压门控钙通道的激活，大幅度反向传播尖峰，提供了一个长期的内向电流，能够产生ADP和爆发的多个动作电位的索马的CA 1锥体神经元。树突状电压门控离子通道通过调节动作电位放电模式从单脉冲放电到爆发放电，深刻地调节CA 1锥体神经元对传入信息的处理和存储。
The role of dendritic voltage-gated ion channels in the generation of action potential bursting was investigated using whole cell patch-clamp recordings from the soma and dendrites of CAI pyramidal neurons located in hippocampal slices of adult rats. Under control conditions somatic current injections evoked single action potentials that were associated with an afterhyperpolarization (AHP). After localized application of 4-aminopyridine (4-AP) to the distal apical dendritic arborization, the same current injections resulted in the generation of an afterdepolarization (ADP) and multiple action potentials. This burst firing was not observed after localized application of 4-AP to the soma/proximal dendrites. The dendritic 4-AP application allowed large-amplitude Na+-dependent action potentials, which were prolonged in duration, to backpropagate into the distal apical dendrites. No change in action potential backpropagation was seen with proximal 4-AP application. Both the ADP and action potential bursting could be inhibited by the bath application of nonspecific concentrations of divalent Ca2+ channel blockers (NiCl and CdCl). Ca2+ channel blockade also reduced the dendritic action potential duration without significantly affecting spike amplitude. Low concentrations of TTX (10-50 nM) also reduced the ability of the CAI neurons to fire in the busting mode. This effect was found to be the result of an inhibition of backpropagating dendritic action potentials and could be overcome through the coordinated injection of transient, large-amplitude depolarizing current into the dendrite. Dendritic current injections were able to restore: the burst firing mode (represented as a large ADP) even in the presence of high concentrations of TTX (300-500 mu M). These data suggest the role of dendritic Na+ channels in bursting is to allow somatic/axonal action potentials to backpropagate into the dendrites where they then activate dendritic Ca2+ channels. Although it appears that most Ca2+ channel subtypes are important in burst generation, blockade of T- and R-type Ca2+ channels by NiCl (75 mu M) inhibited action potential bursting to a greater extent than L-channel (10 mu M nimodipine) or N-, P/Q-type (1 mu M omega-conotoxin MVIIC) Ca2+ channel blockade. This suggest that the Ni-sensitive voltage-gated Ca2+ channels have the most important role in action potential burst generation. In summary, these data suggest that the activation of dendritic voltage-gated Ca2+ channels, by large-amplitude backpropagating spikes, provides a prolonged inward current that is capable of generating an ADP and burst of multiple action potentials in the soma of CA1 pyramidal neurons. Dendritic voltage-gated ion channels profoundly regulate the processing and storage of incoming information in CA1 pyramidal neurons by modulating the action potential firing mode from single spiking to burst firing.