A model of the hyperkalemia produced by metabolic acidosis.

In both humans and animals, mineral acids predictably result in hyperkalemia, whereas plasma K+ remains normal or may even decrease during organic acidosis. The purpose of these studies was to define the mechanism for these effects in the opossum kidney cell, an established epithelial cell line derived from the renal cortex of the opossum. This cell was chosen because the acid/base transport pathways in this cell type are well defined and because it is one of the few cells known to express K/H antiport, the transport pathway that has been proposed to mediate the hyperkalemia of acidosis. Cell K+ at pH 7.4 averaged 988 +/- 48 nmol/mg protein. Relative to this value (100%), cell K+ increased when buffer pH was increased to pH 8.4 with NaOH (108% +/- 3%) and decreased when buffer pH was acidified with HCl to pH 6.4 (93% +/- 4%), producing a highly significant correlation of cell K+ with buffer pH: cell K+ (% of baseline at pH 7.4) = 6.9 (cell pH) + 49 (r = 0.5, P < 0.004). In contrast, acidification of the buffer to pH 6.4 with either butyric or lactic acid increased cell K+ (115% +/- 4% and 110% +/- 2%, respectively, both P < 0.05 v 7.4 or HCl value). Cell pH acidified in response to HCl at a rate of 0.0053 +/- 0.0007 pH U/s, a significantly slower rate than in response to lactic acid or butyric acid (0.0071 +/- 0.0007 and 0.0091 +/- 0.0007 pH U/s, respectively). Unidirectional ouabain-sensitive 42K+ influx was significantly inhibited by HCl acidosis and less so by the organic acids.(ABSTRACT TRUNCATED AT 250 WORDS)