Myo-inositol monophosphatase (IMPase) is a key enzyme in the IP3 signal cascade. It has been designated a potential therapeutic target in bipolar disorder treatment. We previously demonstrated compartment-specific binding of calbindin D28k (CB) to IMPase and its dependency on synaptic activity in spiny dendrites of cerebellar Purkinje neurons by the means of fluorescence recovery after photobleaching. The interaction between CB and IMPase showed a low affinity, indicating a possible role in fast signalling in dendritic microcompartments. The low affinity, however, complicated a further quantification of the interaction, because standard biochemical methods failed to detect and characterize the interaction. Here we show that surface plasmone resonance (SPR) is a suitable method for the analysis of the IMPase-CB interaction. SPR is a highly sensitive technique based on refraction index changes, which reflect binding of protein to an interactor-loaded dextrane surface. With SPR we focussed on binding kinetics and dependencies on Ca2+ , Mg2+ , or Li+ , and confirmed the specific interaction of CB with the IMPase. In contrast to previous biochemical work we found a clear Ca2+ dependence of the interaction, demonstrating that CB is not a simple Ca2+ -buffer but rather a Ca2+ -sensor that modulates IP3 signalling and may be involved in the development and treatment of bipolar disease.