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

The inositol 1,4,5-trisphosphate (InsP) receptor (InsPR) channel is crucial for the generation and modulation of highly specific intracellular Ca signals performing numerous functions in animal cells. However, the single channel behavior during Ca signals of different spatiotemporal scales is not well understood. To elucidate the correlation between the gating dynamics of single InsPRs and spatiotemporal Ca patterns, we simulate a cluster of InsPRs 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 Ca 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 Ca signals. The size, duration and frequency of Ca 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 InsPR to the shaping of different spatiotemporal scales of Ca signals.