Nuclear KATP channels trigger nuclear Ca2+ transients that modulate nuclear function
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Edited by Ramon Latorre, Center for Scientific Studies, Valdivia, Chile, and approved May 22, 2002 (received for review January 23, 2002)
Abstract
Glucose, the principal regulator of endocrine pancreas, has several effects on pancreatic beta cells, including the regulation of insulin release, cell proliferation, apoptosis, differentiation, and gene expression. Although the sequence of events linking glycemia with insulin release is well described, the mechanism whereby glucose regulates nuclear function is still largely unknown. Here, we have shown that an ATP-sensitive K+ channel (KATP) with similar properties to that found on the plasma membrane is also present on the nuclear envelope of pancreatic beta cells. In isolated nuclei, blockade of the KATP channel with tolbutamide or diadenosine polyphosphates triggers nuclear Ca2+ transients and induces phosphorylation of the transcription factor cAMP response element binding protein. In whole cells, fluorescence in situ hybridization revealed that these Ca2+ signals may trigger c-myc expression. These results demonstrate a functional KATP channel in nuclei linking glucose metabolism, nuclear Ca2+ signals, and nuclear function.
Footnotes
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↵ * Present address: Department of Bioengineering, University of Washington, Seattle, WA 98195.
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↵ † To whom reprint requests should be addressed at: Institute of Bioengineering, Miguel Hernández University, San Juan Campus, Carretera Alicante-Valencia Km 87, 03550 Alicante, Spain. E-mail: bernat.soria{at}umh.es.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- KATP,
- ATP-sensitive K+ channel;
- [Ca2+]n,
- nuclear Ca2+ concentration;
- CREB,
- cAMP response element binding protein;
- RT,
- room temperature;
- BODIPY,
- dipyrrometheneboron difluoride;
- nKATP,
- nuclear KATP channel;
- ER,
- endoplasmic reticulum;
- ER/SR,
- endo-sarcoplasmic reticulum;
- RyR,
- ryanodine receptors
- Copyright © 2002, The National Academy of Sciences
