Properties of Inositol 1,4,5-Trisphosphate Receptors in the Nuclei of CNS Neurons in Rats

Abstract

We studied the properties of inositol 1,4,5-trisphosphate receptors (InsP3Rs) in the membranes of the nuclear envelope of CNS neurons in rats. In cells with a maximum level of expression of InsP3Rs, (hippocampal and cerebellar neurons), these receptors are localized predominantly in the inner nuclear membrane. This allows us to hypothesize that the nuclear Ca2+ store is involved in regulation of expression of Ca2+-dependent genes. Applications of agonists of InsP3Rs (InsP3 and Ca2+ in concentrations below 1 μM) evoked rapid activation of channels of InsP3Rs followed by their steady-state activity. Application of [Ca2+] ≥ 1 μM did not influence significantly the characteristics of peak responses, but then the InsP3Rs lose sensitivity almost completely during several seconds. Therefore, the Ca2+ dependence of steady-state activity of these neurons was bell-shaped. Within physiological limits of concentrations of intracellular Ca2+, the peak activity of the above-mentioned receptors was not inhibited by applications of agonists. These findings explain the main contradiction between the data obtained recently by different research groups. At the same time, the basic nature of kinetic properties of InsP3Rs under conditions of various experimental models needs further investigation.