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Ca 2+ oscillations in hepatocytes do not require the modulation of InsP 3 3‐kinase activity by Ca 2+
Author(s) -
Dupont G.,
Koukoui O.,
Clair C.,
Erneux C.,
Swillens S.,
Combettes L.
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03789-4
Subject(s) - catabolism , inositol , cytosol , agonist , chemistry , receptor , biophysics , kinase , biochemistry , endocrinology , biology , enzyme
Receptor‐mediated production of inositol 1,4,5‐trisphosphate (InsP 3 ) initiates Ca 2+ release and is responsible for cytosolic Ca 2+ oscillations. InsP 3 oscillations have also been observed in some cells. One of the enzymes controlling InsP 3 catabolism, the InsP 3 3‐kinase, is stimulated by Ca 2+ ; this regulation is presumably part of the reason for InsP 3 oscillations that have been observed in some cells. Here, we investigate the possible role of Ca 2+ ‐activated InsP 3 catabolism on the characteristics of the InsP 3 ‐induced Ca 2+ oscillations. Numerical simulations show that if it is assumed that the Ca 2+ ‐independent InsP 3 catabolism is predominant, Ca 2+ oscillations remain qualitatively unchanged although the relative amplitude of the oscillations in InsP 3 concentrations becomes minimal. We tested this prediction in hepatocytes by masking the Ca 2+ ‐dependent InsP 3 catabolism by 3‐kinase through the injection of massive amounts of InsP 3 5‐phosphatase, which is not stimulated by Ca 2+ . We find that in such injected hepatocytes, Ca 2+ oscillations generated by modest agonist levels are suppressed, presumably because of the decreased dose in InsP 3 , but that at higher doses of agonist, oscillations reappear, with characteristics similar to those of untreated cells at low agonist doses. Altogether, these results suggest that oscillations in InsP 3 concentration due to Ca 2+ ‐stimulated InsP 3 catabolism do not play a major role for the oscillations in Ca 2+ concentration.