Relative contributions of axonal and somatic Na channels to action potential initiation in cerebellar Purkinje neurons
Relative contributions of axonal and somatic Na channels to action potential initiation in cerebellar Purkinje neurons
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DOI：
10.1523/jneurosci.4664-05.2006
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发表时间：
2006-02-15
影响因子：
5.3
通讯作者：
Raman, IM
中科院分区：
文献类型：
--
作者：
Khaliq, ZM;Raman, IM
神经元的兴奋性很可能受到动作电位起始部位的调节，动作电位起始部位是神经元上最先越过阈值的部位。虽然在许多神经元中起始是轴突的，但在浦肯野细胞中，体细胞电导可以产生自发性动作电位，这表明体周区（索马和/或起始段）有助于锋电位的起始并可能调节放电。为了直接识别钠通道调节显着影响放电的细胞区域，我们测量了出生后14 - 28天小鼠小脑切片中浦肯野细胞的自发和诱发动作电位，同时将药物局部应用于索马/初始段或第一节Ranvier。河豚毒素（TTX）可降低Na电流，β-PMTX可增加Na电流。双躯体和轴突记录表明，尖峰阈值和输入-输出曲线敏感TTX或β-PMTX在围体区域，但在第一个节点的药物不变。然而，当亚饱和TTX降低体周Na通道可用性时，在额外的TTX阻断结通道期间，输入-输出曲线变得较浅，揭示了结Na通道在促进放电中的潜在作用。在体周TTX，轴突未能产生自发或诱发的尖峰列车。相反，胆碱阻断起始段单独改变正常的输入-输出曲线。这些数据表明，虽然第一个节点可靠地遵循动作电位，在浦肯野神经元的尖峰启动发生在初始段。此外，浦肯野细胞的输出依赖于密度，可用性和动力学的perisomatic钠通道，一个特性，可以区分自发放电从静止的神经元。
Neuronal excitability is likely to be regulated by the site of action potential initiation, the location on a neuron that crosses threshold first. Although initiation is axonal in many neurons, in Purkinje cells, somatic conductances can generate spontaneous action potentials, suggesting that the perisomatic region (soma and/or initial segment) contributes to spike initiation and may regulate firing. To identify directly the cellular regions at which Na channel modulation significantly influences firing, we measured spontaneous and evoked action potentials in Purkinje cells in cerebellar slices from postnatal day 14 - 28 mice while applying drugs locally to either the soma/initial segment or the first node of Ranvier. Na currents were decreased by tetrodotoxin ( TTX) or increased by beta-pompilidotoxin (beta-PMTX). Dual somatic and axonal recordings indicated that spike thresholds and input - output curves were sensitive to TTX or beta-PMTX at the perisomatic region but were unchanged by either drug at the first node. When perisomatic Na channel availability was reduced with subsaturating TTX, however, the input - output curve became shallower during additional TTX block of nodal channels, revealing a latent role for nodal Na channels in facilitating firing. In perisomatic TTX, axons failed to generate spontaneous or evoked spike trains. In contrast, choline block of the initial segment alone altered normal input - output curves. The data suggest that, although the first node reliably follows action potentials, spike initiation in Purkinje neurons occurs in the initial segment. Moreover, Purkinje cell output depends on the density, availability, and kinetics of perisomatic Na channels, a characteristic that may distinguish spontaneously firing from quiescent neurons.