Relationships among sodium current, permeability, and Na activities in control and glucocorticoid-stimulated rabbit...

Effects of a potent synthetic glucocorticoid, methylprednisolone (MP), on transepithelial Na transport were examined in rabbit descending colon. Current-voltage (I-V) relations of the amiloride-sensitive apical Na entry pathway were measured in colonic tissues of control and MP-treated (40 mg im for 2 days) animals. Tissues were bathed mucosally by solutions of various Na activities, (Na)m, ranging from 6.2 to 75.6 mM, and serosally by a high K solution. These I-V relations conformed to the "constant field" flux equation permitting determination of the permeability of the apical membrane to Na, PmNa, and the intracellular Na activity, (Na)c. The following empirical relations were observed for both control and MP-treated tissues: Na transport increases hyperbolically with increasing (Na)m obeying simple Michaelis-Mentin kinetics; PmNa decreased hyperbolically with increasing (Na)m, but was unrelated to individual variations in (Na)c; (Na)c increased hyperbolically with (Na)m; both spontaneous and steroid-stimulated variations in Na entry rate could be attributed entirely to parallel variations in PmNa at each mucosal Na activity. Comparison of these empirical, kinetic relations between control and MP-treated tissues revealed: maximal Na current and PmNa were greater in MP tissues, but the (Na)m's at which current and PmNa were half-maximal were markedly reduced; (Na)c was significantly increased in MP tissues at each (Na)m while the (Na)m at half-maximal (Na)c was unchanged. These results provide direct evidence that glucocorticoids cause marked stimulation of Na absorption across rabbit colon primarily by increasing the Na permeability of the apical membrane. While the mechanism for the increased permeability remains to be determined, the altered relation between PmNa and (Na)m suggests possible differences in the conformation or environment of the Na channel in MP-treated tissues.