An increase in nuclear Ca2+ concentration regulates gene transcription by activating nuclear Ca2+-sensetive kinases and phosphatases or by directly affecting Ca2+-binding transcription factors. We have previously reported IP3-activated Ca2+ channels in the inner membrane of cerebellar Purkinje, but not granule neurons (J. Physiol 565:897). Here we studied ion channels in the nuclei from pyramidal neurons of the hippocampal CA1 region. Using the patch-clamp technique we have found IP3-activated ion channels in the inner, but not in the outer nuclear membrane of pyramidal neurons. These channels were selective to Ca2+ (PCa/PK was about 6), had the conductance of ~370 pS in symmetric K+ solution, were characterized by very fast kinetics and weak voltage-dependence. Most patches of the nuclear membrane also contained large conductance (~240 pS) channels selective for monovalent cations with slow kinetics and very high open probability at positive potentials, which were inactivated by large negative potentials (more then -60 mV). These data suggest that the nuclear envelope of hippocampal pyramidal neurons is a Ca2+ store, which release Ca2+ directly into the nucleoplasm.