Glucose-induced oscillations in cytoplasmic free Ca2+ concentration precede oscillations in mitochondrial membrane potential in the pancreatic beta-cell

Using dual excitation and fixed emission fluorescence microscopy, we were a ble to measure changes in cytoplasmic free Ca2+ concentration ([Ca2+](i)) a nd mitochondrial membrane potential simultaneously in the pancreatic beta - cell. The beta -cells were exposed to a combination of the Ca2+ indicator f ura-2/AM and the indicator of mitochondrial membrane potential, rhodamine 1 23 (Rh123). Using simultaneous measurements of mitochondrial membrane poten tial and [Ca2+](i) during glucose stimulation, it was possible to measure t he time lag between the onset of mitochondrial hyperpolarization and change s in [Ca2+](i). Glucose-induced oscillations in [Ca2+](i) were followed by transient depolarizations of mitochondrial membrane potential. These result s are compatible with a model in which nadirs in [Ca2+](i) oscillations are generated by a transient, Ca2+-induced inhibition of mitochondrial metabol ism resulting in a temporary fall in the cytoplasmic ATP/ADP ratio, opening of plasma membrane K-ATP channels, repolarization of the plasma membrane, and thus transient closure of voltage-gated L-type Ca2+ channels.