Changes in intracellular pH (pH_in) and intracellular calcium concentration [Ca²⁺]_i play a major role in signal transduction leading to cell growth, differentiation and transformation. In some tumor cell lines, vacuolar (V-type) H⁺-adenosine triphosphatases (ATPases) are important in pH_in regulation. To clarify the neoplastic nature and endothelial origin of Kaposi sarcoma (KS), pH_in and [Ca²⁺]_i and the functional expression of V-type H⁺-ATPases were evaluated in cultured endothelial marker-positive KS cells derived from AIDS-KS skin lesions as compared to human umbilical vein endothelial cells (HUVEC). Human skin fibroblasts (HSF) were also examined. Cells were examined using fluorescence spectroscopy with the pH_in indicator SNARF-1 and the [Ca²⁺]i indicator Fura-2. We found that whereas pH_in recovery from acid loading occurred in the absence of Na⁺ and HCO^–₃ in HUVEC and HSF, KS cells did not recover. Moreover, removal of extracellular Na⁺ had no effect on [Ca²⁺]_i in HUVEC, but transiently increased [Ca²⁺]_i in KS cells and HSF. This [Ca²⁺]_i spike was unaffected by Ca²⁺-free medium, suggesting that it is not due to Na⁺/Ca²⁺ exchange. In addition, use of K⁺-containing and K⁺-free medium to mimic depolarization or hyperpolarization, which may occur during Na⁺ removal, did not cause [Ca²⁺]_i changes. The [Ca²⁺]_i levels were also not sensitive to intracellular acidification but were specifically sensitive to [Na⁺]. Thus, KS cells differ from normal endothelial cells in the kinetics of pH_in recovery to acid loads, and in the presence of a specific [Na⁺]-sensitive intracellular Ca²⁺ pool. These differences in ion homeostasis indicate that these cell types are not developmentally related or that alterations in ion transport are a part of the etiology of the KS lesion.

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