Yavorsky Volodymyr A, Rozumna Nataliia M, Lukyanetz Elena A
Department of Biophysics of Ion Channels, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Front Cell Neurosci. 2023 Apr 13;17:1132092. doi: 10.3389/fncel.2023.1132092. eCollection 2023.
One of the signs of Alzheimer's disease (AD) is the formation of β-amyloid plaques, which ultimately lead to the dysfunction of neurons with subsequent neurodegeneration. Although extensive researches have been conducted on the effects of different amyloid conformations such as oligomers and fibrils on neuronal function in isolated cells and circuits, the exact contribution of extracellular beta-amyloid on neurons remains incompletely comprehended. In our experiments, we studied the effect of β-amyloid peptide (Aβ1-42) on the action potential (APs) generation in isolated CA1 hippocampal neurons in perforated patch clamp conditions. Our findings demonstrate that Aβ1-42 affects the generation of APs differently in various hippocampal neurons, albeit with a shared effect of enhancing the firing response of the neurons within a minute of the start of Aβ1-42 application. In the first response type, there was a shift of 20-65% toward smaller values in the firing threshold of action potentials in response to inward current. Conversely, the firing threshold of action potentials was not affected in the second type of response to the application of Aβ1-42. In these neurons, Aβ1-42 caused a moderate increase in the frequency of spiking, up to 15%, with a relatively uniform increase in the frequency of action potentials generation regardless of the level of input current. Obtained data prove the absence of direct short-term negative effect of the Aβ1-42 on APs generation in neurons. Even with increasing the APs generation frequency and lowering the neurons' activation threshold, neurons were functional. Obtained data can suggest that only the long-acting presence of the Aβ1-42 in the cell environment can cause neuronal dysfunction due to a prolonged increase of APs firing and predisposition to this process.
阿尔茨海默病（AD）的症状之一是β-淀粉样蛋白斑块的形成，这最终会导致神经元功能障碍并随后发生神经退行性变。尽管已经对不同淀粉样蛋白构象（如寡聚体和原纤维）对分离细胞和回路中神经元功能的影响进行了广泛研究，但细胞外β-淀粉样蛋白对神经元的确切作用仍未完全理解。在我们的实验中，我们研究了β-淀粉样肽（Aβ1-42）在穿孔膜片钳条件下对分离的CA1海马神经元动作电位（APs）产生的影响。我们的研究结果表明，Aβ1-42在不同的海马神经元中对APs的产生有不同的影响，尽管在应用Aβ1-42开始后的一分钟内，神经元的放电反应有共同的增强作用。在第一种反应类型中，响应内向电流时动作电位的放电阈值向较小值偏移了20-65%。相反，在对Aβ1-42应用的第二种反应类型中，动作电位的放电阈值不受影响。在这些神经元中，Aβ1-42使放电频率适度增加，高达15%，无论输入电流水平如何，动作电位产生频率相对均匀地增加。获得的数据证明Aβ1-42对神经元中APs的产生没有直接的短期负面影响。即使增加了APs的产生频率并降低了神经元的激活阈值，神经元仍具有功能。获得的数据表明，只有Aβ1-42在细胞环境中的长期存在才会由于APs放电的长期增加和对该过程的易感性而导致神经元功能障碍。
