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Forskolin stabilizes epsilon subunit-containing acetylcholine receptors
1Yale University School of Medicine, Department of Cellular and Molecular Physiology, New Haven, CT 06510.
Brain Research. Molecular Brain Research
|October 1, 1994
Summary
Forskolin stabilizes adult acetylcholine receptors (AChRs) containing the epsilon-subunit, but not fetal gamma-AChRs. This supports epsilon-AChRs being the slow-degrading population in muscle.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Muscle acetylcholine receptors (AChRs) exist in fetal (gamma-AChR) and adult (epsilon-AChR) forms with distinct half-lives.
- Two AChR populations, rapidly and slowly degrading, coexist postsynaptically after denervation.
- Forskolin and cAMP analogues increase the half-life of slow-degrading AChRs in cultured muscle cells.
Purpose of the Study:
- To investigate forskolin's effect on the cell surface half-lives of gamma-AChRs and epsilon-AChRs.
- To determine if epsilon-subunit phosphorylation mediates forskolin's effect on AChR stability.
Main Methods:
- Stable expression of mouse gamma-AChRs, epsilon-AChRs, and alpha beta delta complexes in mouse fibroblasts.
- Treatment with forskolin and analysis of cell surface half-lives.
- In vivo phosphorylation analysis of the epsilon-subunit.
Main Results:
- Forskolin did not significantly affect the half-life of gamma-AChRs or alpha beta delta complexes.
- Forskolin stabilized epsilon-AChRs by approximately twofold.
- Epsilon-subunit phosphorylation increased with forskolin treatment, and this effect was reversible.
Conclusions:
- Forskolin selectively stabilizes adult epsilon-AChRs, not fetal gamma-AChRs.
- Results support the hypothesis that epsilon-AChRs constitute the slowly degrading population and gamma-AChRs the rapidly degrading population.
- Epsilon-subunit phosphorylation may play a role in regulating AChR stability.