Inositol, 1,4,5-trisphosphate (IP3) is produced by stimulating cells caused by neurotransmitters, neurotrophic factors, etc. IP3 acts upon the IP3 receptor (IP3 activating Ca²⁺ channel) in the intracellular Ca²⁺ store to induce the release of Ca²⁺ into the cytoplasm. It is deeply involved in the neural function (synaptic plasticity, neurite extension, etc.) and neural diseases (epileptic seizure, neuronal cell death, etc.). The activation of the IP3 receptor causes not only a transient increase in cytoplasmic Ca²⁺ but also results in repeated positive and negative regulation feedback by the released Ca²⁺, (diphasic control at low Ca²⁺ and high Ca²⁺, with a peak at approximately 0.5μ M). This results in spatial-temporal Ca²⁺ dynamics such as in Ca²⁺ waves and Ca²⁺ oscillations. However, much remains unknown as to these mechanisms at the molecular level.

In the recent research, we have reconstructed parified type 1 IP3 receptors into an artificial planar lipid bilayers to examine at single channel-decording levels, and have clarified that in the absence of calmodulin the Ca²⁺ basically acts positively on the IP3 receptors but in the presence of calmodulin negatively in the high Ca²⁺ domain. In other words, we have demonstrated that the high Ca²⁺ sensor of the IP3 receptor is the calmodulin, which exists abundantly in the brain and that the Ca²⁺ bound calmodulin probably inactivates the IP3 receptor by directly linking with the IP3 receptor.

These results have been achieved following joint research undertaken together with the Institute of Medical Science, University of Tokyo, the Tokyo Medical and Dental College and the Japan Science and Technology Corporation (JST).