Mode switching of Inositol 1,4,5-trisphosphate receptor channel shapes the Spatiotemporal scales of Ca²⁺ signals

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• 作者：Ghanim Ullah ; Aman Ullah
• 关键词：Ca 2+ signaling ; Inositol 1 ; 4 ; 5 ; trisphosphate receptor ; Modal gating ; Multi ; scales
• 刊名：Journal of Biological Physics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：42
• 期：4
• 页码：507-524
• 全文大小：1,259 KB
• 刊物类别：Physics and Astronomy
• 刊物主题：Physics
  Biophysics and Biomedical Physics
  Condensed Matter
  Statistical Physics
  Polymer Sciences
  Bioinformatics
  Neurosciences
  
• 出版者：Springer Netherlands
• ISSN：1573-0689
• 卷排序：42

文摘

The inositol 1,4,5-trisphosphate (InsP₃) receptor (InsP₃R) channel is crucial for the generation and modulation of highly specific intracellular Ca2+ signals performing numerous functions in animal cells. However, the single channel behavior during Ca2+ signals of different spatiotemporal scales is not well understood. To elucidate the correlation between the gating dynamics of single InsP₃Rs and spatiotemporal Ca2+ patterns, we simulate a cluster of InsP₃Rs under varying ligand concentrations and extract comprehensive gating statistics of all channels during events of different sizes and durations. Our results show that channels gating predominantly in the low activity mode with negligible occupancy of intermediate and high modes leads to single channel Ca2+ release event blips. Increasing occupancies of intermediate and high modes results in events with increasing size. When the channel has more than 50% probability of gating in the intermediate and high modes, the cluster generates very large puffs that would most likely result in global Ca2+ signals. The size, duration and frequency of Ca2+ signals all increase linearly with the total probability of channel gating in the intermediate and high modes. To our knowledge, this is the first study that quantitatively relates the modal characteristics of InsP₃R to the shaping of different spatiotemporal scales of Ca2+ signals.