Chang Linda W, Spitzer Nicholas C
Department of Bioengineering and Neurobiology Section, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, California 92093-0357, USA.
J Neurosci. 2009 Jun 17;29(24):7877-85. doi: 10.1523/JNEUROSCI.4264-08.2009.
Different types and patterns of spontaneous electrical activity drive many aspects of neuronal differentiation. Neurons in the developing Xenopus spinal cord exhibit calcium spikes, which regulate gene transcription and neurotransmitter specification. The ionic currents necessary for spike production have been described. However, the mechanisms that generate the onset of this activity and the basis of its regulation remain unclear. Although signaling molecules appear to act on plasma membrane receptors to trigger calcium spike activity, other mechanisms for spontaneous calcium spike regulation may exist as well. Here, we analyze the developmental expression of the Na(+), K(+)-ATPase beta3 subunit in Xenopus tropicalis embryos and show that its levels are downregulated at a time during embryonic development that coincides with the onset of prominent calcium spike activity in spinal neurons. Inhibition of an earlier increase in beta3 expression leads to more depolarized resting membrane potentials and results in later reduction of spike activity. This suppression of beta3 levels also reduces expression of the store-operated calcium channel subunit, Orai1. These findings suggest that the Na(+), K(+)-ATPase plays a role in initiating calcium spike activity and regulating calcium homeostasis.
不同类型和模式的自发电活动驱动着神经元分化的许多方面。非洲爪蟾发育中的脊髓神经元表现出钙峰，其调节基因转录和神经递质的特化。已描述了产生峰所需的离子电流。然而，产生这种活动起始的机制及其调节基础仍不清楚。尽管信号分子似乎作用于质膜受体以触发钙峰活动，但可能还存在其他自发钙峰调节机制。在这里，我们分析了热带爪蟾胚胎中Na(+)、K(+)-ATP酶β3亚基的发育表达，结果表明，在胚胎发育过程中，其水平在与脊髓神经元中显著钙峰活动起始时间一致时被下调。抑制β3表达的早期增加会导致静息膜电位更去极化，并导致后期峰活动减少。β3水平的这种抑制也会降低储存操纵性钙通道亚基Orai1的表达。这些发现表明，Na(+)、K(+)-ATP酶在启动钙峰活动和调节钙稳态中发挥作用。
