The nuclear envelope is composed of two membranes deliminating a perinuclear space which displays functional properties similar to those of a Ca2+-storing compartment, ATP-driven Ca2+ uptake and InsP(3)-induced Ca2+ release processes have been described in isolated nuclei, Recently, it was reported that cADP-ribose and InsP(3) can trigger a nucleoplasmic Ca2+ increase. It was hypothesized that the inner nuclear membrane possesses Ca2+ channels that are regulated by ryanodine or InsP(3), Radio-ligand binding assays and Western blot experiments were performed in order to investigate their presence in sheep cardiac and rat liver nuclear envelopes, Ryanodine receptors (RyR) were not detected in liver nuclear envelopes by either binding assay or Western blot analysis, However, cardiac nuclear envelopes were found to retain a very low level of specific ryanodine binding, which was not detected on immune-blots obtained with three types of isoform-specific RyR antibodies, In contrast, nuclear InsP(3)-binding sites were consistently detected in both cardiac and liver nuclear envelopes. Altogether, these results provide evidence for the major contributor InsP(3)-gated Ca2+ channels in control of Ca2+ release from the perinuclear space in liver and cardiac cells. (C) 1997 Federation of European Biochemical Societies.