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Identification of three isoforms of the InsP 3 receptor in human myometrial smooth muscle

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Abstract

The mechanisms responsible for the mobilisation of Ca2+ from intracellular stores sensitive to inositol trisphosphate (InsP 3) were studied in saponin-permeabilised human myometrial cells in which the sarcoplasmic reticulum was pre-loaded with45Ca2+. InsP 3-induced45Ca2+ release was measured over the InsP 3 concentration range of 100 nM to 100 μM and showed a graded response. InsP 3-induced45Ca2+ release was inhibited by heparin (20–40 μg/ml) but not significantly affected by caffeine. The Ca2+ sensitivity of InsP 3-induced Ca2+ release was measured under conditions which were designed to exclude interference with Ca2+ released by the ryanodine receptor/channel complex. The data showed a bell-shaped relationship with the InsP 3 receptor (InsP 3R) functional at 10 nM, becoming maximally activated at 300 nM but inhibited at 10 μM Ca2+. Messenger RNA encoding for three isoforms of InsP 3R, type I, II and type III, was shown to be present. The relative expression levels of these messengers were obtained by ratio-PCR analysis and the levels of expression of the different isoforms were found to differ between individual patients.

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Authors and Affiliations

  1. Department of Physiological Sciences, The Medical School, The University, NE2 4HH, Newcastle upon Tyne, UK

    Joanna M. Morgan & James I. Gillespie

  2. Laboratorium voor Fysiologie, K.U. Leuven, Campus Gasthuisberg, B-3000, Leuven, Belgium

    Humbert De Smedt

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  1. Joanna M. Morgan
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  2. Humbert De Smedt
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  3. James I. Gillespie
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Morgan, J.M., De Smedt, H. & Gillespie, J.I. Identification of three isoforms of the InsP 3 receptor in human myometrial smooth muscle. Pflugers Arch. 431, 697–705 (1996). https://doi.org/10.1007/BF02253832

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  • DOI: https://doi.org/10.1007/BF02253832

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