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Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing
Molecular Brain ( IF 3.3 ) Pub Date : 2021-07-17 , DOI: 10.1186/s13041-021-00813-7
Fernando R Fernandez 1 , Mircea C Iftinca 2, 3 , Gerald W Zamponi 2, 3, 4 , Ray W Turner 3, 4, 5
Affiliation  

T-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

中文翻译:

模拟 T 型钙通道介导的突发放电中温度和 Cav3 亚型依赖性变化

T 型钙通道是神经元兴奋性的重要调节剂。哺乳动物大脑表达三种 T 型通道亚型(Cav3.1、Cav3.2 和 Cav3.3),具有受温度严格调节的不同生物物理特性。在这里,我们测试了在表达特定 Cav3 通道亚型的减少放电神经元模型中温度如何影响尖峰输出的影响。建模数据显示,对接近静止状态的基线自发放电的影响很小,但由于窗口电流或激活/恢复时间常数的差异,与 Cav3.2 或 Cav3.3 相比,Cav3.1 的反弹突发放电频率显着增加。Cav3.2 降低的反应可以优化其在外周组织中表达的活性,比 Cav3.1 或 Cav3 更容易受到温度变化的影响。3 个通道在大脑中显着表达。因此,这些测试揭示了神经元放电行为的各个方面严重依赖于温度和 T 型钙通道亚型。
更新日期:2021-07-18
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