Open AccessNuclear K ATP channels trigger nuclear Ca 2+ transients that modulate nuclear function
Author(s) -
Iván Quesada,
Juan M. Rovira,
Franz Martı́n,
Enrique Roche,
Ángel Nadal,
Bernat Soria
Publication year - 2002
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.142039299
Subject(s) - tolbutamide , nuclear transport , cell nucleus , nuclear export signal , biology , microbiology and biotechnology , transcription factor , nuclear protein , chemistry , insulin , biochemistry , endocrinology , gene , cytoplasm
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 (K(ATP)) 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 K(ATP) channel with tolbutamide or diadenosine polyphosphates triggers nuclear Ca(2+) transients and induces phosphorylation of the transcription factor cAMP response element binding protein. In whole cells, fluorescence in situ hybridization revealed that these Ca(2+) signals may trigger c-myc expression. These results demonstrate a functional K(ATP) channel in nuclei linking glucose metabolism, nuclear Ca(2+) signals, and nuclear function.