Regulation of InsP(3)-mediated Ca2+ release by CaMKII in Xenopus oocytes

Inhibition of calmodulin (CaM) sensitizes Ca2+ release mediated by D-myo-in ositol (1,4,5)-trisphosphate (InsP(3)) in Xenopus oocytes, which results in spontaneous Ca2+-dependent Cl- current oscillations or in a shift of the c oncentration threshold for lysophosphatidic acid (LPA) by a tenfold factor. The oscillatory currents appear at a low initial Ca2+ concentration and wi thout any significant increase in the inositol phosphate (InsPs) concentrat ions. These data led us to rule out the direct involvement of CaM, as well as the implied involvement of InsP(3) 3-kinase, The response to intracellul ar injection of the non-metabolizable InsP(3) analog 3-deoxy-3-fluoro InsP( 3) (InsP(3)-F) is obviously affected by previous treatment with CaM inhibit ory peptide. Furthermore, these effects have been consistently obtained wit h specific CaMKII inhibitors such as KN-93 and AIP. CaM plays a key role in the Ca2+-dependent inactivation of type I InsP(3) receptors. The experimen ts presented hereby allow us to postulate that CaM could also exert its inh ibitory effect through CaMKII in a way that does not involve InsP(3) metabo lism regulation. It is concluded that CaMKII could participate in Ca2+-evok ed inhibition of InsP(3)-mediated Ca2+ release by inhibiting the InsP(3) re ceptor.