Parallel changes in nuclear and cytosolic calcium in mouse pancreatic β-cells

In the neuroendocrine pancreatic β-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 β-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 β-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.