Nuclear KATP channels trigger nuclear Ca(2+) transients that modulate nuclear function.
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.
Quesada
Ivan
I
Institute of Bioengineering, Miguel Hernández University, San Juan Campus, 03550 Alicante, Spain.
Rovira
Juan M
JM
Martin
Franz
F
Roche
Enrique
E
Nadal
Angel
A
Soria
Bernat
B
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D016259:Genes, myc; D005947:Glucose / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D014044:Tolbutamide / Q000494:pharmacology
D017362:Cyclic AMP Response Element-Binding Protein; D015226:Dinucleoside Phosphates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005947:Glucose