Insulin activates furosemide-sensitive K⁺ and Cl^- uptake system in BC₃H1 cells

Insulin augments the activity of Na⁺-K⁺-adenosinetriphosphatase (ATPase) in skeletal muscles. This study shows that when furosemide- and bumetanide- inhibitable ⁸⁶Rb⁺ uptake is measured in the skeletal muscle-like BC₃H1 cell line, insulin and insulin-like growth factor I (IGF-I) activate a loop diuretic-sensitive K⁺ and Cl transport system but have no effect on Na⁺- K⁺-ATPase. The insulin-stimulated K⁺ transport system is extracellular Na⁺ concentration ([Na⁺](o)) independent and extracellular Cl^- concentration ([Cl^-](o)) dependent. Na⁺-independent K⁺-Cl^- cotransport systems have been identified in other cells, but their sensitivity to insulin or growth factors has not been described. The affinities of the insulin-stimulated K⁺ uptake in BC₃H1 cells for K⁺ (0.9 ± 0.1 mM) and loop diuretics (5.9 x 10^{- 7} and 10^-7 M for furosemide and bumetanide, respectively) are higher than those of K⁺-Cl^- cotransporters in other cells. Thus the insulin-stimulated K⁺ and Cl^- transport system in BC₃H1 seems kinetically different from K⁺- Cl^- cotransporters in other cells. Insulin and IGF-I may activate a unique K⁺-Cl^- cotransporter or activate a [Na⁺](o)-independent K⁺-Cl^- cotransporter mode of Na⁺-K⁺-Cl^- cotransporter in BC₃H1 cells.