Regulation of Cell Functions by Ca2+ Oscillation

  • Masamitsu Iino
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 592)


Since the initial discovery of the regulatory role of intracellular Ca2+ signals in skeletal muscle contraction (Ebashi and Endo, 1968; Ebashi et al., 1969), the list of cellular functions that are regulated by Ca2+ signals has expanded. Now, it is recognized that intracellular Ca2+ signals are involved in the regulation of various cell functions including fertilization, secretion, transcription, immunity, learning and memory (Berridge et al., 2000). One of the striking features of Ca2+ signals is that they display complex spatiotemporal distributions such as Ca2+ waves and oscillations. An oscillatory change in Ca2+ concentration was first observed in skinned fiber experiments by Endo and collaborators in 1970 (Endo et al., 1970). When skinned skeletal muscle fibers were immersed in a solution mimicking intracellular conditions and caffeine was added to the solution at millimolar concentrations, the skinned fibers underwent periodic contractions because of the periodic release of Ca2+ from the sarcoplasmic reticulum, in the absence of membrane potential changes. With the advent of methods of measuring intracellular Ca2+ concentration, Ca2+ oscillation has been observed in many types of intact cell. In 1986, Cobbold and collaborators (Woods et al., 1986) observed Ca2+ oscillation in agonist-stimulated hepatocytes using aequorin, a Ca2+-sensitive luminescent protein. The introduction of fluorescent Ca2+ indicators further facilitated the observation of intracellular Ca2+ transients (Tsien, 1988). Initially, the physiological significance of Ca2+ oscillation was not fully appreciated, because they were observed only in cell lines or in isolated cells.


Nuclear Translocation Myosin Light Chain Myosin Light Chain Phosphatase Smooth Muscle Myosin Light Chain Myosin Light Chain Phosphatase Activity 
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26.5. References

  1. Babcock, D. F., Herrington, J., Goodwin, P. C., Park, Y. B., and Hille, B., 1997, Mitochondrial participation in the intracellular Ca2+ network, J. Cell Biol. 136:833–844.PubMedCrossRefGoogle Scholar
  2. Berridge, M. J., 1993, Inositol trisphosphate and calcium signaling, Nature 361:315–325.PubMedCrossRefGoogle Scholar
  3. Berridge, M. J., Lipp, P., and Bootman, M. D., 2000, The versatility and universality of calcium signalling, Nat. Rev. Mol. Cell Biol. 1:11–21.PubMedCrossRefGoogle Scholar
  4. Dolmetsch, R. E., Xu, K., and Lewis, R. S., 1998, Calcium oscillations increase the efficiency and specificity of gene expression, Nature 392:933–936.PubMedCrossRefGoogle Scholar
  5. Ebashi, S., and Endo, M., 1968, Calcium ion and muscle contraction, Prog. Biophys. Mol. Biol. 18:123–183.PubMedCrossRefGoogle Scholar
  6. Ebashi, S., Endo, M., and Ohtsuki, I., 1969, Control of muscle contraction, Q. Rev. Biophys. 2:351–384.PubMedCrossRefGoogle Scholar
  7. Endo, M., Tanaka, M., and Ogawa, Y., 1970, Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibres, Nature 228:34–36.PubMedCrossRefGoogle Scholar
  8. Goldbeter, A., Dupont, G., and Berridge, M. J., 1990, Minimal model for signal-induced Ca2+oscillations and for their frequency encoding through protein phosphorylation, Proc. Natl. Acad. Sci. USA 87:1461–1465.PubMedCrossRefGoogle Scholar
  9. Iino, M., 1990, Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci, J. Gen. Physiol. 95:1103–1122.PubMedCrossRefGoogle Scholar
  10. Iino, M., Kasai, H., and Yamazawa, T., 1994, Visualization of neural control of intracellular Ca2+ concentration in single vascular smooth muscle cells in situ, EMBO J 13:5026–5031.PubMedGoogle Scholar
  11. Ishii, K., Hirose, K., and Iino, M., 2006, Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations, EMBO Rep. 7:390–396.PubMedCrossRefGoogle Scholar
  12. Ito, M., Nakano, T., Erdodi, F., and Hartshorne, D. J., 2004, Myosin phosphatase: structure, regulation and function. Mol. Cell. Biochem. 259:197–209.PubMedCrossRefGoogle Scholar
  13. Jouaville, L. S., Ichas, F., Holmuhamedov, E. L., Camacho, P., and Lechleiter, J. D., 1995, Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes, Nature 377:438–441.PubMedCrossRefGoogle Scholar
  14. Li, W., Llopis, J., Whitney, M., Zlokarnik, G., and Tsien, R. Y., 1998, Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression, Nature 392:936–941.PubMedCrossRefGoogle Scholar
  15. Mitsui, T., Kitazawa, T., and Ikebe, M., 1994, Correlation between high temperature dependence of smooth muscle myosin light chain phosphatase activity and muscle relaxation rate, J. Biol. Chem. 269:5842–5848.PubMedGoogle Scholar
  16. Miyakawa, T., Mizushima, A., Hirose, K., Yamazawa, T., Bezprozvanny, I., Kurosaki, T., and Iino, M., 2001, Ca2+-sensor region of IP3 receptor controls intracellular Ca2+ signaling, EMBO J. 20:1674–1680.PubMedCrossRefGoogle Scholar
  17. Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., and Pozzan, T. 1998, Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses, Science 280:1763–1766.PubMedCrossRefGoogle Scholar
  18. Somlyo, A. P., and Somlyo, A. V., 2003, Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase, Physiol. Rev. 83:1325–1358.PubMedGoogle Scholar
  19. Tomida, T., Hirose, K., Takizawa, A., Shibasaki, F., and Iino, M., 2003, NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation, EMBO J. 22:3825–3832.PubMedCrossRefGoogle Scholar
  20. Tsien, R. Y., 1988, Fluorescence measurement and photochemical manipulation of cytosolic free calcium, Trends Neurosci. 11:419–424.PubMedCrossRefGoogle Scholar
  21. Woods, N. M., Cuthbertson, K. S., and Cobbold, P. H., 1986, Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes, Nature 319:600–602.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Masamitsu Iino
    • 1
  1. 1.Department of Pharmacology, Graduate School of MedicineThe University of TokyoTokyoJapan

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