Bioluminescence imaging of nuclear calcium oscillations in intact pancreatic islets of Langerhans from the mouse

The stimulus-secretion coupling for insulin secretion by pancreatic β cells in response to high glucose involves synchronic cytosolic calcium oscillations driven by bursting electrical activity. Calcium inside organelles can regulate additional functions, but analysis of subcellular calcium signals, specially at the single cell level, has been hampered for technical constrains. Here we have monitored nuclear calcium oscillations by bioluminescence imaging of targeted aequorin in individual cells within intact islets of Langerhans as well as in the whole islet. We find that glucose generates a pattern of nuclear calcium oscillations resembling those found in the cytosol. Some cells showed synchronous nuclear calcium oscillations suggesting that the islet of Langerhans may also regulate the activation of Ca2+-responsive nuclear processes, such as gene transcription, in a coordinated, synchronic manner. The nuclear Ca2+ oscillations are due to bursting electrical activity and activation of plasma membrane voltage-gated Ca2+ channels with little or no contribution of calcium release from the intracellular Ca2+ stores. Irregularities in consumption of aequorins suggests that depolarization may generate formation of steep Ca2+ gradients in both the cytosol and the nucleus, but further research is required to investigate the role of such high [Ca2+] microdomains.