Molecular Basis and Physiological Functions of Dynamic Ca2+ Signalling in Smooth Muscle Cells

  1. Derek J. Chadwick Organizer and
  2. Jamie A. Goode
  1. Masamitsu Iino

Published Online: 7 OCT 2008

DOI: 10.1002/0470853050.ch11

Role Of The Sarcoplasmic Reticulum In Smooth Muscle: Novartis Foundation Symposium 246

Role Of The Sarcoplasmic Reticulum In Smooth Muscle: Novartis Foundation Symposium 246

How to Cite

Iino, M. (2008) Molecular Basis and Physiological Functions of Dynamic Ca2+ Signalling in Smooth Muscle Cells, in Role Of The Sarcoplasmic Reticulum In Smooth Muscle: Novartis Foundation Symposium 246 (eds D. J. Chadwick and J. A. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470853050.ch11

Author Information

  1. Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 15 JUN 2002

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470844793

Online ISBN: 9780470853054

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Summary

We have visualized Ca2+ signals in smooth muscle cells mediated by the release of Ca2+ from intracellular Ca2+ stores and studied their underlying molecular basis. Ca2+ signals in smooth muscle cells within intact arterial tissues show diverse spatiotemporal patterns: Ca2+ waves and oscillations were induced by agonist stimulation or by sympathetic nerve stimulation. We also found spontaneous Ca2+ oscillations with low amplitudes (Ca2+ ripples) that were observed in the absence of extrinsic stimulation. These dynamic spatiotemporal patterns were generated by Ca2+ release via the inositol-1,4,5-trisphosphate (InsP3) receptor (InsP3R). We then studied the molecular basis of such complex Ca2+ signalling patterns. The activity of InsP3R is regulated by the cytoplasmic Ca2+ concentration. The sensitivity of InsP3R to Ca2+ provides feedback regulation of the Ca2+ release, which may be important for the generation of Ca2+ signalling patterns. A series of site-specific mutagenesis experiments in type 1 InsP3R allowed us to identify glutamate at position 2100 as the Ca2+ sensor. Substitution of the amino acid by aspartic acid resulted in a 10-fold decrease in Ca2+ sensitivity. In cells expressing the mutant InsP3R,Ca2+ release spikes and oscillations were inhibited, indicating the role of the Ca2+ sensitivity of InsP3R in the generation of spatiotemporal patterns of Ca2+ signals.