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

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.