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

Abstract

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.