Oscillations in calcium released from intracellular stores regulate cellular responses to increases in intracellular calcium concentration [Ca 2+ ] I . The amplitude of the calcium spikes can be independent of agonist concentration, but the frequency of the spikes is often a function of agonist concentration. Zhu et al. electroporated HeLa cells to deliver specific inositol phosphate compounds or antibodies against phosphoinositol kinase, which altered the intracellular concentrations of specific polyphosphoinositides, and monitored calcium oscillations in response to histamine with the calcium-sensitive dye Fluo-3. Their data are consistent with inositol (1,3,4,5) tetraphosphate (Ins(1,3,4,5)P 4 ) being the frequency regulator in vivo and with Ins(1,3,4,5)P 4 being produced through the action of inositol (1,4,5) trisphosphate kinase (IP3K) on inositol (1,4,5) trisphosphate. Furthermore, IP3K is a calcium/calmodulin-activated enzyme providing a possible mechanism for the oscillatory nature of the activity of IP3K. Zhu, D.-M., Tekle, E., Huang, C.Y., and Chock, P.B. (2000) Inositol tetrakisphosphate as a frequency regulator in calcium oscillations in HeLa cells. J. Biol.Chem. 275 : 6063-6066. [Abstract] [Full Text]