Yeast can proliferate in environments containing very high Ca2+ primarily due to the activity of vacuolar Ca2+ transporters Pmc1 and Vcx1. Yeast mutants lacking these transporters fail to grow in high Ca2+ environments, but growth can be restored by small increases in environmental Mg2+. Low extracellular Mg2+ appeared to competitively inhibit novel Ca2+ influx pathways and to diminish the concentration of free Ca2+ in the cytoplasm, as judged from the luminescence of the photoprotein aequorin. These Mg2+-sensitive Ca2+ influx pathways persisted in yvc1 cch1 double mutants. Based on mathematical models of the aequorin luminescence traces, we propose the existence in yeast of at least two Ca2+ transporters that undergo rapid feedback inhibition in response to elevated cytosolic free Ca2+ concentration. Finally, we show that Vcx1 helps return cytosolic Ca2+ toward resting levels after shock with high extracellular Ca2+ much more effectively than Pmc1 and that calcineurin, a protein phosphatase regulator of Vcx1 and Pmc1, had no detectable effects on these factors within the first few minutes of its activation. Therefore, computational modeling of Ca2+ transport and signaling in yeast can provide important insights into the dynamics of this complex system.

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