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Inositol trisphosphate, calcium and muscle contraction
A P Somlyo1, J W Walker, Y E Goldman
1Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6083.
Summary
This study reveals that G-proteins regulate intracellular calcium release through both inositol trisphosphate (Ins(1,4,5)P3)-dependent and independent pathways in smooth muscle. Mitochondria do not play a significant role in regulating cytoplasmic calcium levels in muscle cells.
Area of Science:
- Cell Biology
- Muscle Physiology
- Biochemistry
Background:
- Intracellular calcium (Ca2+) storage and release are critical for muscle contraction.
- Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) is a known second messenger involved in Ca2+ signaling.
- The precise roles of different organelles and G-proteins in muscle Ca2+ regulation require further elucidation.
Purpose of the Study:
- To identify the primary intracellular calcium-storing organelles in muscle cells.
- To investigate the role of Ins(1,4,5)P3 in muscle contraction.
- To determine the involvement of G-proteins in intracellular Ca2+ release mechanisms.
Main Methods:
- Electron probe X-ray microanalysis (EPMA) to identify Ca2+ storage sites.
- Laser photolysis of 'caged' Ins(1,4,5)P3 to study its rapid release.
- Studies on saponin-permeabilized smooth muscle to assess G-protein function.
- Measurement of contraction latency and force development.
Main Results:
- The sarcoplasmic reticulum (SR) is the major Ca2+ source in smooth and striated muscle; endoplasmic reticulum in non-muscle cells.
- Mitochondria play a negligible role in regulating cytoplasmic Ca2+.
- G-protein activation in smooth muscle leads to Ca2+ release via both Ins(1,4,5)P3-dependent and independent pathways.
- Ins(1,4,5)P3 is unlikely to mediate excitation-contraction coupling in striated muscle but is compatible with pharmacomechanical coupling in smooth muscle.
Conclusions:
- G-protein activation can trigger Ca2+ release through at least two distinct mechanisms in smooth muscle.
- The sarcoplasmic reticulum is the primary intracellular Ca2+ store in muscle.
- Ins(1,4,5)P3 likely acts as a physiological messenger in smooth muscle pharmacomechanical coupling, but not in striated muscle excitation-contraction coupling.