The role of phosphoinositide metabolism in Ca2+ signalling of skeletal muscle cells |
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Affiliation: | 1. Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Division of Cystic Fibrosis, Charité – Universitätsmedizin, Berlin, Germany;2. Department of Radiology including Pediatric Radiology, Charité – Universitätsmedizin, Berlin, Germany;3. German Rheumatism Research Centre, Berlin, Germany;4. Department of Biostatistics and Clinical Epidemiology, Charité – Universitätsmedizin, Berlin, Germany;5. Hochschule Osnabrück, University of Applied Sciences, Germany;6. Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Division of Rheumatology, Charité – Universitätsmedizin, Berlin, Germany;7. Division Cystic Fibrosis, CF Center Westbrandenburg, Clinic Westbrandenburg, Potsdam, Germany;1. Laboratory for Machine Tools and Production Engineering (WZL) of RWTH Aachen University, Campus-Boulevard 30, 52074 Aachen, Germany |
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Abstract: | - 1.1. The mobilization of Ca2+ from intracellular stores by d-myo-inositol 1,4,5-triphosphate[Ins(1,4,5)P3] is now widely accepted as the primary link between plasma membrane receptors that stimulate phospholipase C and the subsequent increase in intracellular free Ca2+ that occurs when such receptors are activated (Berridge, 1993). Since the observations of VoIpe et al. (1985) which showed that Ins(1,4,5)P3 could induce Ca2+ release from isolated terminal cisternae membranes and elicit contracture of chemically skinned muscle fibres, research has focused on the role of Ins(1,4,5)P3 in the generation of SR Ca2+ transients and in the mechanism of excitation-contraction coupling (EC-coupling).
- 2.2. The mechanism of signal transduction at the triadic junction during EC-coupling is unknown. Asymmetric charge movement and mechanical coupling between highly specialized triadic proteins has been proposed as the primary mechanism for voltage-activated generation of SR Ca2+ signals and subsequent contraction. Ins(1,4,5)P3 has also been proposed as the major signal transduction molecule for the generation of the primary Ca2+ transient produced during EC-coupling.
- 3.3. Investigations on the generation of Ca2+ transients by Ins(1,4,5)P3 have been conducted on ion channels incorporated into lipid bilayers, skinned and intact fibres and isolated membrane vesicles. Ins(1,4,5)P3 induces SR Ca2+ release and the enzymes responsible for its synthesis and degradation are present in muscle tissue. However, the sensitivity of the Ca2+ release mechanism to Ins(l,4,5)P3 is highly dependent on experimental conditions and on membrane potential.
- 4.4. While Ins(1,4,5)P3 may not be the major signal transduction molecule for the generation of the primary Ca2+ signal produced during voltage-activated contraction, this inositol polyphosphate may play a functional role as a modulator of EC-coupling and/or of the processes of myoplasmic Ca2+ regulation occurring on a time scale of seconds, during the events of contraction.
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