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 able to measure changes in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and mitochondrial membrane potential simultaneously in the pancreatic beta-cell. The beta-cells were exposed to a combination of the Ca(2+) indicator fura-2/AM and the indicator of mitochondrial membrane potential, rhodamine 123 (Rh123). Using simultaneous measurements of mitochondrial membrane potential and [Ca(2+)](i) during glucose stimulation, it was possible to measure the time lag between the onset of mitochondrial hyperpolarization and changes in [Ca(2+)](i). Glucose-induced oscillations in [Ca(2+)](i) were followed by transient depolarizations of mitochondrial membrane potential. These results are compatible with a model in which nadirs in [Ca(2+)](i) oscillations are generated by a transient, Ca(2+)-induced inhibition of mitochondrial metabolism 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 Ca(2+) channels.