Parallel changes in nuclear and cytosolic calcium in mouse pancreatic beta-cells.
In the neuroendocrine pancreatic beta-cell, elevations in intracellular Ca2+ lead to insulin secretion and the initiation of gene transcription. However, the relationship between cytosolic and nuclear Ca2+ in these cells is unknown. The Ca2+ permeability of the nuclear membrane would therefore determine if Ca2+ could play a direct role in Ca2+-dependent nuclear processes. Using confocal fluorescence microscopy with the ratiometric Ca2+ indicator indo-1 and carefully correcting for compartmentalized indicator, we now demonstrate that there is no difference between the nuclear Ca2+ concentration and the cytosolic Ca2+ concentration ([Ca2+]c) in the resting beta-cell. Slow Ca2+ oscillations induced by glucose, fast oscillations induced by glucagon-like peptide-1 and responses to potassium and carbachol all indicate that changes in cytosolic Ca2+ are reflected within the nucleus. We conclude that there are no restrictions on Ca2+ entry into the nucleus of the pancreatic beta-cell subsequent to increases in [Ca2+]c. This implies that any signal involved in increasing [Ca2+]c, and thereby insulin release, may also promote nuclear Ca2+-induced gene transcription.
Brown
G R
GR
Department of Molecular Medicine, The Rolf Luft Center for Diabetes Research, Karolinska Institute, Karolinska Hospital L6B:01, S-171 76 Stockholm, Sweden.
Köhler
M
M
Berggren
P O
PO
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D004396:Coloring Agents; D003600:Cytosol / Q000378:metabolism*; D007211:Indoles; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D018613:Microscopy, Confocal
D004396:Coloring Agents; D007211:Indoles; C048960:indo-1; D002118:Calcium