We investigated the influence of nutrients on spontaneous cytosolic calcium oscillations in InR1-G9 glucagonoma cells, a model for pancreatic alpha-cells. The oscillations depended on calcium release from stores and on calcium influx, partly through voltage-dependent calcium channels. Oscillations required the presence of at least 1 mM glucose, 50 microM alanine, or 50 microM glutamine, but were terminated by higher nutrient concentrations (40 mM glucose, or above 2 mM alanine or glutamine). The effects depended on the metabolism of the nutrients. Glutamine and alanine hyperpolarized the cells. This effect was inhibited (glutamine) or attenuated (alanine) by 1 mM ouabain. Our findings suggest that [Ca2+]i regulation in alpha-cells is dominated by slow oscillations induced by a lack of metabolic energy, resulting in decreased calcium export and storage, as well as increased calcium influx, partly due to depolarization caused by reduced sodium pump activity. These processes, leading to an elevated cytosolic calcium concentration, may mediate oscillations by calcium-induced calcium release from intracellular stores.