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Cyclic ADP-ribose increases Ca2+ removal in smooth muscle.
Karen N Bradley1, Susan Currie, Debbi MacMillan
1Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.
Journal of Cell Science
|September 11, 2003
Summary
Cyclic ADP ribose (cADPR) does not release calcium via ryanodine receptors in smooth muscle cells. Instead, cADPR influences calcium removal from the cytoplasm, possibly through the sarcolemma calcium pump.
Area of Science:
- Cellular physiology
- Calcium signaling
- Muscle cell biology
Background:
- Calcium release via ryanodine receptors (RyRs) is crucial for cell signaling and cellular functions.
- Cyclic ADP ribose (cADPR) is proposed to modulate RyR activity, but its mechanism is debated.
- Smooth muscle cells possess RyRs but lack FKBP12.6, a protein potentially targeted by cADPR.
Purpose of the Study:
- To investigate the effect of cADPR on calcium signaling in smooth muscle cells lacking FKBP12.6.
- To determine if cADPR modulates calcium release through RyRs in these cells.
Main Methods:
- Utilized caged cADPR to study calcium signaling in voltage-clamped smooth muscle cells.
- Administered caffeine to assess RyR function.
- Performed western blots to investigate cADPR binding to FKBP proteins.
Main Results:
- cADPR failed to release calcium or enhance caffeine-induced responses in colonic myocytes.
- Caffeine effectively modulated RyR activity in the same cells.
- cADPR did not bind to FKBP proteins, and introducing FKBP12.6 did not restore cADPR activity.
- cADPR accelerated cytoplasmic calcium removal, an effect inhibited by 8-bromo-cADPR.
Conclusions:
- cADPR does not modulate calcium release via RyRs in smooth muscle cells.
- cADPR influences cytoplasmic calcium levels, likely by affecting calcium removal mechanisms such as the sarcolemma calcium pump.